{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T01:15:36Z","timestamp":1790558136830,"version":"4.1.0"},"reference-count":190,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2023,1,23]],"date-time":"2023-01-23T00:00:00Z","timestamp":1674432000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82072508"],"award-info":[{"award-number":["82072508"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82272464"],"award-info":[{"award-number":["82272464"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Musculoskeletal disorders, including fractures, scoliosis, heterotopic ossification, osteoporosis, osteoarthritis, disc degeneration, and muscular injury, etc., can occur at any stage of human life. Understanding the occurrence and development mechanism of musculoskeletal disorders, as well as the changes in tissues and cells during therapy, might help us find targeted treatment methods. Single-cell techniques provide excellent tools for studying alterations at the cellular level of disorders. However, the application of these techniques in research on musculoskeletal disorders is still limited. This review summarizes the current single-cell and spatial omics used in musculoskeletal disorders. Cell isolation, experimental methods, and feasible experimental designs for single-cell studies of musculoskeletal system diseases have been reviewed based on tissue characteristics. Then, the paper summarizes the latest findings of single-cell studies in musculoskeletal disorders from three aspects: bone and ossification, joint, and muscle and tendon disorders. Recent discoveries about the cell populations involved in these diseases are highlighted. Furthermore, the therapeutic responses of musculoskeletal disorders, especially single-cell changes after the treatments of implants, stem cell therapies, and drugs are described. Finally, the application potential and future development directions of single-cell and spatial omics in research on musculoskeletal diseases are discussed.<\/jats:p>","DOI":"10.3390\/ijms24032271","type":"journal-article","created":{"date-parts":[[2023,1,24]],"date-time":"2023-01-24T01:29:45Z","timestamp":1674523785000},"page":"2271","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Application of Single-Cell and Spatial Omics in Musculoskeletal Disorder Research"],"prefix":"10.3390","volume":"24","author":[{"given":"Site","family":"Feng","sequence":"first","affiliation":[{"name":"School of Medicine, Tsinghua University, Beijing 100084, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6796-0637","authenticated-orcid":false,"given":"Jiahao","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Science, Beijing 100730, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingjing","family":"Tian","sequence":"additional","affiliation":[{"name":"Medical Science Research Center, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7532-8981","authenticated-orcid":false,"given":"Sheng","family":"Lu","sequence":"additional","affiliation":[{"name":"The Key Laboratory of Digital Orthopaedics of Yunnan Provincial, Department of Orthopedic Surgery, The First People\u2019s Hospital of Yunnan Province, The Affiliated Hospital of Kunming University of Science and Technology, Kunming 650032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9025-2014","authenticated-orcid":false,"given":"Yu","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Science, Beijing 100730, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Esther, R.J. (2021). Clinical Foundations of Musculoskeletal Medicine: A Manual for Medical Students, Springer International Publishing.","DOI":"10.1007\/978-3-030-42894-5"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"696","DOI":"10.1038\/s41580-020-00279-w","article-title":"Mechanisms of bone development and repair","volume":"21","author":"Salhotra","year":"2020","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1038\/nrd.2015.16","article-title":"Single-cell analysis tools for drug discovery and development","volume":"15","author":"Heath","year":"2016","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"604","DOI":"10.1007\/s11926-012-0288-9","article-title":"Intersection of inflammation and herbal medicine in the treatment of osteoarthritis","volume":"14","author":"Mobasheri","year":"2012","journal-title":"Curr. Rheumatol. Rep."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s40141-020-00306-z","article-title":"Focused extracorporeal shockwave therapy in physical medicine and rehabilitation","volume":"9","author":"Crevenna","year":"2021","journal-title":"Curr. Phys. Med. Rehabil. Rep."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1038\/nrg3228","article-title":"Genetics of osteoporosis from genome-wide association studies: Advances and challenges","volume":"13","author":"Richards","year":"2012","journal-title":"Nat. Rev. Genet."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"237","DOI":"10.47102\/annals-acadmedsg.V40N5p237","article-title":"Orthopaedic implant technology: Biomaterials from past to future","volume":"40","author":"Wang","year":"2011","journal-title":"Ann. Acad. Med. Singap."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1207","DOI":"10.1002\/jbmr.3802","article-title":"The Unmixing Problem: A Guide to Applying Single-Cell RNA Sequencing to Bone","volume":"34","author":"Greenblatt","year":"2019","journal-title":"J. Bone Miner. Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"189","DOI":"10.3389\/fcell.2019.00189","article-title":"A revised perspective of skeletal stem cell biology","volume":"7","author":"Ambrosi","year":"2019","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Aboul-Soud, M.A.M., Alzahrani, A.J., and Mahmoud, A. (2021). Induced Pluripotent Stem Cells (iPSCs)-Roles in Regenerative Therapies, Disease Modelling and Drug Screening. Cells, 10.","DOI":"10.3390\/cells10092319"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1080\/1061186X.2018.1464011","article-title":"Recent advances in kartogenin for cartilage regeneration","volume":"27","author":"Cai","year":"2019","journal-title":"J. Drug Target."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1038\/nmeth.1315","article-title":"mRNA-Seq whole-transcriptome analysis of a single cell","volume":"6","author":"Tang","year":"2009","journal-title":"Nat. Methods"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"e13161","DOI":"10.1111\/cpr.13161","article-title":"Advances in single-cell sequencing and its application to musculoskeletal system research","volume":"55","author":"Zhang","year":"2022","journal-title":"Cell Prolif."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1007\/s11914-022-00735-w","article-title":"Single-Cell RNA Sequencing: Unravelling the Bone One Cell at a Time","volume":"20","author":"Chai","year":"2022","journal-title":"Curr. Osteoporos. Rep."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"13939","DOI":"10.1038\/s41598-020-70786-5","article-title":"Multi-omic single cell analysis resolves novel stromal cell populations in healthy and diseased human tendon","volume":"10","author":"Kendal","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1038\/nmeth.4380","article-title":"Simultaneous epitope and transcriptome measurement in single cells","volume":"14","author":"Stoeckius","year":"2017","journal-title":"Nat. Methods"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e160702","DOI":"10.1172\/jci.insight.160702","article-title":"A single-cell mass cytometry platform to map the effects of preclinical drugs on cartilage homeostasis","volume":"7","author":"Sahu","year":"2022","journal-title":"JCI Insight"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1126\/science.1198704","article-title":"Single-cell mass cytometry of differential immune and drug responses across a human hematopoietic continuum","volume":"332","author":"Bendall","year":"2011","journal-title":"Science"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"e2103087118","DOI":"10.1073\/pnas.2103087118","article-title":"Spatial transcriptomics reveals a role for sensory nerves in preserving cranial suture patency through modulation of BMP\/TGF-\u03b2 signaling","volume":"118","author":"Tower","year":"2021","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"18975","DOI":"10.1038\/s41598-019-55441-y","article-title":"Exploring inflammatory signatures in arthritic joint biopsies with Spatial Transcriptomics","volume":"9","author":"Carlberg","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1038\/s41586-021-03634-9","article-title":"Exploring tissue architecture using spatial transcriptomics","volume":"596","author":"Rao","year":"2021","journal-title":"Nature"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1202","DOI":"10.1016\/j.cell.2015.05.002","article-title":"Highly Parallel Genome-wide Expression Profiling of Individual Cells Using Nanoliter Droplets","volume":"161","author":"Macosko","year":"2015","journal-title":"Cell"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1187","DOI":"10.1016\/j.cell.2015.04.044","article-title":"Droplet barcoding for single-cell transcriptomics applied to embryonic stem cells","volume":"161","author":"Klein","year":"2015","journal-title":"Cell"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"14049","DOI":"10.1038\/ncomms14049","article-title":"Massively parallel digital transcriptional profiling of single cells","volume":"8","author":"Zheng","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1007\/978-1-4939-9240-9_9","article-title":"Single-Cell Tagged Reverse Transcription (STRT-Seq)","volume":"1979","author":"Natarajan","year":"2019","journal-title":"Methods Mol. Biol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"708","DOI":"10.1038\/s41587-020-0497-0","article-title":"Single-cell RNA counting at allele and isoform resolution using Smart-seq3","volume":"38","author":"Ziegenhain","year":"2020","journal-title":"Nat. Biotechnol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1038\/nbt.2282","article-title":"Full-length mRNA-Seq from single-cell levels of RNA and individual circulating tumor cells","volume":"30","author":"Luo","year":"2012","journal-title":"Nat. Biotechnol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1038\/s41467-017-02659-x","article-title":"Single-cell RNA-seq of rheumatoid arthritis synovial tissue using low-cost microfluidic instrumentation","volume":"9","author":"Stephenson","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1038\/nri.2017.76","article-title":"Single-cell RNA sequencing to explore immune cell heterogeneity","volume":"18","author":"Papalexi","year":"2018","journal-title":"Nat. Rev. Immunol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"20097","DOI":"10.1074\/jbc.RA119.011506","article-title":"High-resolution genome-wide expression analysis of single myofibers using SMART-Seq","volume":"294","author":"Blackburn","year":"2019","journal-title":"J. Biol. Chem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"534","DOI":"10.1038\/s41592-022-01409-2","article-title":"Museum of spatial transcriptomics","volume":"19","author":"Moses","year":"2022","journal-title":"Nat. Methods"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1007\/BF01003828","article-title":"The laser in the Lowry technique for microdissection of freeze-dried tissue slices","volume":"8","author":"Bielser","year":"1976","journal-title":"Histochem. J."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"586","DOI":"10.1038\/s41587-020-0472-9","article-title":"Multiplex digital spatial profiling of proteins and RNA in fixed tissue","volume":"38","author":"Merritt","year":"2020","journal-title":"Nat. Biotechnol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1126\/science.aaf2403","article-title":"Visualization and analysis of gene expression in tissue sections by spatial transcriptomics","volume":"353","author":"Vickovic","year":"2016","journal-title":"Science"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"eaaa6090","DOI":"10.1126\/science.aaa6090","article-title":"Spatially resolved, highly multiplexed RNA profiling in single cells","volume":"348","author":"Chen","year":"2015","journal-title":"Science"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"eaat5691","DOI":"10.1126\/science.aat5691","article-title":"Three-dimensional intact-tissue sequencing of single-cell transcriptional states","volume":"361","author":"Wang","year":"2018","journal-title":"Science"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1038\/s41576-021-00444-7","article-title":"Temporal modelling using single-cell transcriptomics","volume":"23","author":"Ding","year":"2022","journal-title":"Nat. Rev. Genet."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1038\/s41586-019-0969-x","article-title":"The single-cell transcriptional landscape of mammalian organogenesis","volume":"566","author":"Cao","year":"2019","journal-title":"Nature"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"e117","DOI":"10.1093\/nar\/gkw430","article-title":"TSCAN: Pseudo-time reconstruction and evaluation in single-cell RNA-seq analysis","volume":"44","author":"Ji","year":"2016","journal-title":"Nucleic Acids Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1186\/s12864-018-4772-0","article-title":"Slingshot: Cell lineage and pseudotime inference for single-cell transcriptomics","volume":"19","author":"Street","year":"2018","journal-title":"BMC Genom."},{"key":"ref_41","first-page":"e54","article-title":"SLICE: Determining cell differentiation and lineage based on single cell entropy","volume":"45","author":"Guo","year":"2017","journal-title":"Nucleic Acids Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1186\/s13059-019-1663-x","article-title":"PAGA: Graph abstraction reconciles clustering with trajectory inference through a topology preserving map of single cells","volume":"20","author":"Wolf","year":"2019","journal-title":"Genome Biol."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Roux de B\u00e9zieux, H., Van den Berge, K., Street, K.N., and Dudoit, S. (2021). Trajectory inference across multiple conditions with condiments: Differential topology, progression, differentiation, and expression. bioRxiv.","DOI":"10.1101\/2021.03.09.433671"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2442","DOI":"10.1038\/s41467-018-04696-6","article-title":"Uncovering pseudotemporal trajectories with covariates from single cell and bulk expression data","volume":"9","author":"Campbell","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1038\/s41596-018-0103-9","article-title":"Pathway enrichment analysis and visualization of omics data using g:Profiler, GSEA, Cytoscape and EnrichmentMap","volume":"14","author":"Reimand","year":"2019","journal-title":"Nat. Protoc."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"15545","DOI":"10.1073\/pnas.0506580102","article-title":"Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profiles","volume":"102","author":"Subramanian","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1186\/1471-2105-14-7","article-title":"GSVA: Gene set variation analysis for microarray and RNA-seq data","volume":"14","author":"Castelo","year":"2013","journal-title":"BMC Bioinform."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.coisb.2021.03.007","article-title":"The landscape of cell-cell communication through single-cell transcriptomics","volume":"26","author":"Almet","year":"2021","journal-title":"Curr. Opin. Syst. Biol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1088","DOI":"10.1038\/s41467-021-21246-9","article-title":"Inference and analysis of cell-cell communication using CellChat","volume":"12","author":"Jin","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1484","DOI":"10.1038\/s41596-020-0292-x","article-title":"CellPhoneDB: Inferring cell-cell communication from combined expression of multi-subunit ligand-receptor complexes","volume":"15","author":"Efremova","year":"2020","journal-title":"Nat. Protoc."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"809918","DOI":"10.3389\/fcell.2021.809918","article-title":"Recent Advances in Single-Cell View of Mesenchymal Stem Cell in Osteogenesis","volume":"9","author":"Shen","year":"2021","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"e1184","DOI":"10.1002\/jsp2.1184","article-title":"Single-cell RNA Seq reveals cellular landscape-specific characteristics and potential etiologies for adolescent idiopathic scoliosis","volume":"4","author":"Yang","year":"2021","journal-title":"JOR Spine"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"742","DOI":"10.1038\/s41422-021-00467-z","article-title":"Dissecting human embryonic skeletal stem cell ontogeny by single-cell transcriptomic and functional analyses","volume":"31","author":"He","year":"2021","journal-title":"Cell Res."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"109302","DOI":"10.1016\/j.intimp.2022.109302","article-title":"Single-cell RNA sequencing analysis dissected the osteo-immunology microenvironment and revealed key regulators in osteoporosis","volume":"113","author":"Wang","year":"2022","journal-title":"Int. Immunopharmacol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1038\/s41413-021-00163-z","article-title":"Spatially defined single-cell transcriptional profiling characterizes diverse chondrocyte subtypes and nucleus pulposus progenitors in human intervertebral discs","volume":"9","author":"Gan","year":"2021","journal-title":"Bone Res."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1136\/annrheumdis-2017-212863","article-title":"Single-cell RNA-seq analysis reveals the progression of human osteoarthritis","volume":"78","author":"Ji","year":"2019","journal-title":"Ann. Rheum. Dis."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"10868","DOI":"10.1038\/s41598-020-67730-y","article-title":"Synovial cell cross-talk with cartilage plays a major role in the pathogenesis of osteoarthritis","volume":"10","author":"Chou","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1186\/s13395-020-00236-3","article-title":"A reference single-cell transcriptomic atlas of human skeletal muscle tissue reveals bifurcated muscle stem cell populations","volume":"10","author":"Spector","year":"2020","journal-title":"Skelet. Muscle"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1177\/00220345221084200","article-title":"Identification of periosteal osteogenic progenitors in jawbone","volume":"101","author":"Ding","year":"2022","journal-title":"J. Dent. Res."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1186\/s12860-022-00429-2","article-title":"Systematic study of single-cell isolation from musculoskeletal tissues for single-sell sequencing","volume":"23","author":"Gao","year":"2022","journal-title":"BMC Mol. Cell Biol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1007\/978-1-0716-0989-7_7","article-title":"Specimen Preparation for Single-Cell Sequencing Analysis of Skeletal Cells","volume":"2221","author":"Debnath","year":"2021","journal-title":"Methods Mol. Biol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1981","DOI":"10.1002\/jbmr.4052","article-title":"Single-Cell RNA Sequencing of Calvarial and Long-Bone Endocortical Cells","volume":"35","author":"Ayturk","year":"2020","journal-title":"J. Bone Miner. Res."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1915","DOI":"10.1016\/j.cell.2019.04.040","article-title":"A cellular taxonomy of the bone marrow stroma in homeostasis and leukemia","volume":"177","author":"Baryawno","year":"2019","journal-title":"Cell"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1038\/s41536-022-00225-8","article-title":"A murine model of large-scale bone regeneration reveals a selective requirement for Sonic Hedgehog","volume":"7","author":"Serowoky","year":"2022","journal-title":"NPJ Regen. Med."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"eabl5716","DOI":"10.1126\/sciadv.abl5716","article-title":"NGF-p75 signaling coordinates skeletal cell migration during bone repair","volume":"8","author":"Xu","year":"2022","journal-title":"Sci. Adv."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1016\/bs.ctdb.2019.02.002","article-title":"Mechanistic insights into skeletal development gained from genetic disorders","volume":"133","author":"Yip","year":"2019","journal-title":"Curr. Top. Dev. Biol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/j.matbio.2022.04.006","article-title":"Hedgehog signaling orchestrates cartilage-to-bone transition independently of Smoothened","volume":"110","author":"Wang","year":"2022","journal-title":"Matrix Biol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"eabd0536","DOI":"10.1126\/scisignal.abd0536","article-title":"Activin A promotes the development of acquired heterotopic ossification and is an effective target for disease attenuation in mice","volume":"14","author":"Mundy","year":"2021","journal-title":"Sci. Signal."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1261","DOI":"10.1002\/art.39030","article-title":"Identification of a Prg4-expressing articular cartilage progenitor cell population in mice","volume":"67","author":"Kozhemyakina","year":"2015","journal-title":"Arthritis Rheumatol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"dev200249","DOI":"10.1242\/dev.200249","article-title":"Hyaline cartilage differentiation of fibroblasts in regeneration and regenerative medicine","volume":"149","author":"Yu","year":"2022","journal-title":"Development"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1038\/s41419-021-03832-3","article-title":"Comparison of the major cell populations among osteoarthritis, Kashin-Beck disease and healthy chondrocytes by single-cell RNA-seq analysis","volume":"12","author":"Wang","year":"2021","journal-title":"Cell Death Dis."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"104258","DOI":"10.1016\/j.ebiom.2022.104258","article-title":"Single cell RNA-seq analysis identifies ferroptotic chondrocyte cluster and reveals TRPV1 as an anti-ferroptotic target in osteoarthritis","volume":"84","author":"Lv","year":"2022","journal-title":"EBioMedicine"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"928","DOI":"10.1038\/s41590-019-0378-1","article-title":"Defining inflammatory cell states in rheumatoid arthritis joint synovial tissues by integrating single-cell transcriptomics and mass cytometry","volume":"20","author":"Zhang","year":"2019","journal-title":"Nat. Immunol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1324","DOI":"10.1016\/j.joca.2021.06.010","article-title":"Single-cell RNA-seq analysis identifies unique chondrocyte subsets and reveals involvement of ferroptosis in human intervertebral disc degeneration","volume":"29","author":"Zhang","year":"2021","journal-title":"Osteoarthr. Cartil."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"833420","DOI":"10.3389\/fcell.2021.833420","article-title":"Single-Cell RNA-Seq Analysis Reveals Macrophage Involved in the Progression of Human Intervertebral Disc Degeneration","volume":"9","author":"Ling","year":"2021","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Cherif, H., Mannarino, M., Pacis, A.S., Ragoussis, J., Rabau, O., Ouellet, J.A., and Haglund, L. (2022). Single-Cell RNA-Seq Analysis of Cells from Degenerating and Non-Degenerating Intervertebral Discs from the Same Individual Reveals New Biomarkers for Intervertebral Disc Degeneration. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23073993"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"3670","DOI":"10.1038\/s41467-018-06068-6","article-title":"Dynamics of cellular states of fibro-adipogenic progenitors during myogenesis and muscular dystrophy","volume":"9","author":"Malecova","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"3583","DOI":"10.1016\/j.celrep.2020.02.067","article-title":"Single-Cell Analysis of the Muscle Stem Cell Hierarchy Identifies Heterotypic Communication Signals Involved in Skeletal Muscle Regeneration","volume":"30","author":"Laurilliard","year":"2020","journal-title":"Cell Rep."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"dev174177","DOI":"10.1242\/dev.174177","article-title":"Single cell analysis of adult mouse skeletal muscle stem cells in homeostatic and regenerative conditions","volume":"146","author":"Juan","year":"2019","journal-title":"Development"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"100993","DOI":"10.1016\/j.isci.2020.100993","article-title":"Temporal Dynamics and Heterogeneity of Cell Populations during Skeletal Muscle Regeneration","volume":"23","author":"Oprescu","year":"2020","journal-title":"iScience"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1490","DOI":"10.1038\/s41556-019-0417-z","article-title":"A Tppp3+Pdgfra+ tendon stem cell population contributes to regeneration and reveals a shared role for PDGF signalling in regeneration and fibrosis","volume":"21","author":"Harvey","year":"2019","journal-title":"Nat. Cell Biol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1075","DOI":"10.1136\/annrheumdis-2020-219335","article-title":"Novel self-amplificatory loop between T cells and tenocytes as a driver of chronicity in tendon disease","volume":"80","author":"Cafaro","year":"2021","journal-title":"Ann. Rheum. Dis."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.actbio.2018.09.031","article-title":"Current state of fabrication technologies and materials for bone tissue engineering","volume":"80","author":"Wubneh","year":"2018","journal-title":"Acta Biomater."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"2668","DOI":"10.2353\/ajpath.2009.090185","article-title":"Septoclast deficiency accompanies postnatal growth plate chondrodysplasia in the toothless (tl) osteopetrotic, colony-stimulating factor-1 (CSF-1)-deficient rat and is partially responsive to CSF-1 injections","volume":"175","author":"Gartland","year":"2009","journal-title":"Am. J. Pathol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1177\/43.5.7730591","article-title":"The septoclast, a cathepsin B-rich cell involved in the resorption of growth plate cartilage","volume":"43","author":"Lee","year":"1995","journal-title":"J. Histochem. Cytochem."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1007\/s00418-018-1653-1","article-title":"Origin and development of septoclasts in endochondral ossification of mice","volume":"149","author":"Bando","year":"2018","journal-title":"Histochem. Cell Biol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1038\/s41467-022-28142-w","article-title":"Mesenchymal stromal cell-derived septoclasts resorb cartilage during developmental ossification and fracture healing","volume":"13","author":"Sivaraj","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"5137","DOI":"10.1172\/JCI128428","article-title":"Fracture repair requires TrkA signaling by skeletal sensory nerves","volume":"129","author":"Li","year":"2019","journal-title":"J. Clin. Investig."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"2723","DOI":"10.1016\/j.celrep.2016.08.002","article-title":"NGF-TrkA Signaling by Sensory Nerves Coordinates the Vascularization and Ossification of Developing Endochondral Bone","volume":"16","author":"Tomlinson","year":"2016","journal-title":"Cell Rep."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"470","DOI":"10.4252\/wjsc.v7.i2.470","article-title":"CD271 as a marker to identify mesenchymal stem cells from diverse sources before culture","volume":"7","year":"2015","journal-title":"World J. Stem Cells"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1038\/s41413-018-0021-z","article-title":"The art of building bone: Emerging role of chondrocyte-to-osteoblast transdifferentiation in endochondral ossification","volume":"6","author":"Aghajanian","year":"2018","journal-title":"Bone Res."},{"key":"ref_92","unstructured":"Breeland, G., Sinkler, M.A., and Menezes, R.G. (2022). StatPearls, StatPearls Publishing."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"101077","DOI":"10.1016\/j.siny.2019.101077","article-title":"Post-natal bone physiology","volume":"25","author":"Ali","year":"2020","journal-title":"Semin. Fetal Neonatal Med."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.matbio.2019.12.004","article-title":"Single cell RNA-sequencing reveals cellular heterogeneity and trajectories of lineage specification during murine embryonic limb development","volume":"89","author":"Kelly","year":"2020","journal-title":"Matrix Biol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"6709","DOI":"10.1038\/ncomms7709","article-title":"Ptch1 and Gli regulate Shh signalling dynamics via multiple mechanisms","volume":"6","author":"Cohen","year":"2015","journal-title":"Nat. Commun."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"116075","DOI":"10.1016\/j.bone.2021.116075","article-title":"Genetic animal models of scoliosis: A systematical review","volume":"152","author":"Lv","year":"2021","journal-title":"Bone"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"1327","DOI":"10.1007\/s00402-017-2756-1","article-title":"Current insights into the aetiology of adolescent idiopathic scoliosis","volume":"137","author":"Latalski","year":"2017","journal-title":"Arch. Orthop. Trauma Surg."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1016\/j.stemcr.2019.08.006","article-title":"Lgr5 and Col22a1 Mark Progenitor Cells in the Lineage toward Juvenile Articular Chondrocytes","volume":"13","author":"Feng","year":"2019","journal-title":"Stem Cell Rep."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"dev185777","DOI":"10.1242\/dev.185777","article-title":"A single cell transcriptional atlas of early synovial joint development","volume":"147","author":"Bian","year":"2020","journal-title":"Development"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"e10172","DOI":"10.1002\/jbm4.10172","article-title":"Heterotopic ossification: A comprehensive review","volume":"3","author":"Meyers","year":"2019","journal-title":"JBMR PLUS"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1007\/s00256-005-0958-z","article-title":"Heterotopic ossification: A review","volume":"34","author":"McCarthy","year":"2005","journal-title":"Skelet. Radiol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"1229","DOI":"10.1111\/1440-1681.13025","article-title":"Challenges of heterotopic ossification-Molecular background and current treatment strategies","volume":"45","author":"Drela","year":"2018","journal-title":"Clin. Exp. Pharmacol. Physiol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"5428","DOI":"10.1111\/jcmm.15240","article-title":"Heterotopic ossification of tendon and ligament","volume":"24","author":"Zhang","year":"2020","journal-title":"J. Cell. Mol. Med."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"606","DOI":"10.2106\/JBJS.17.01484","article-title":"The relationship between dural ossification and spinal stenosis in thoracic ossification of the ligamentum flavum","volume":"101","author":"Yu","year":"2019","journal-title":"J. Bone Jt. Surg. Am."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.mehy.2016.03.011","article-title":"A potential mechanism of dural ossification in ossification of ligamentum flavum","volume":"92","author":"Li","year":"2016","journal-title":"Med. Hypotheses"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1186\/s12860-020-00280-3","article-title":"Identification of the molecular mechanism and diagnostic biomarkers in the thoracic ossification of the ligamentum flavum using metabolomics and transcriptomics","volume":"21","author":"Li","year":"2020","journal-title":"BMC Mol. Cell Biol."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"eabn2138","DOI":"10.1126\/sciadv.abn2138","article-title":"RSPO2 defines a distinct undifferentiated progenitor in the tendon\/ligament and suppresses ectopic ossification","volume":"8","author":"Tachibana","year":"2022","journal-title":"Sci. Adv."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1038\/s41574-019-0282-7","article-title":"A road map for understanding molecular and genetic determinants of osteoporosis","volume":"16","author":"Yang","year":"2020","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1038\/nrrheum.2016.48","article-title":"The genetics of bone mass and susceptibility to bone diseases","volume":"12","author":"Karasik","year":"2016","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1016\/j.ejphar.2015.03.028","article-title":"Animal models for osteoporosis","volume":"759","author":"Komori","year":"2015","journal-title":"Eur. J. Pharmacol."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"2294","DOI":"10.1073\/pnas.1220811110","article-title":"Estrogen receptor-\u03b1 in osteocytes is important for trabecular bone formation in male mice","volume":"110","author":"Windahl","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.bone.2013.12.005","article-title":"Estrogen receptor \u03b1 in osteocytes regulates trabecular bone formation in female mice","volume":"60","author":"Kondoh","year":"2014","journal-title":"Bone"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1002\/jbmr.2082","article-title":"Female mice lacking estrogen receptor-alpha in osteoblasts have compromised bone mass and strength","volume":"29","author":"Melville","year":"2014","journal-title":"J. Bone Miner. Res."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1096\/fj.12-213587","article-title":"Inactivation of estrogen receptor \u03b1 in bone-forming cells induces bone loss in female mice","volume":"27","author":"Gu","year":"2013","journal-title":"FASEB J."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1172\/JCI65910","article-title":"Estrogen receptor-\u03b1 signaling in osteoblast progenitors stimulates cortical bone accrual","volume":"123","author":"Almeida","year":"2013","journal-title":"J. Clin. Investig."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1210\/me.2009-0354","article-title":"The estrogen receptor-alpha in osteoclasts mediates the protective effects of estrogens on cancellous but not cortical bone","volume":"24","author":"Almeida","year":"2010","journal-title":"Mol. Endocrinol."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1016\/j.cell.2007.07.025","article-title":"Estrogen prevents bone loss via estrogen receptor alpha and induction of Fas ligand in osteoclasts","volume":"130","author":"Nakamura","year":"2007","journal-title":"Cell"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1016\/S8756-3282(97)00016-1","article-title":"Short-term effects of corticosteroids on trabecular bone remodeling in old ewes","volume":"20","author":"Chavassieux","year":"1997","journal-title":"Bone"},{"key":"ref_119","first-page":"E136","article-title":"Prednisone-induced osteopenia in beagles: Variable effects mediated by differential suppression of bone formation","volume":"263","author":"Quarles","year":"1992","journal-title":"Am. J. Physiol."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"396","DOI":"10.3109\/17453674.2010.483986","article-title":"Characterization of a rabbit osteoporosis model induced by ovariectomy and glucocorticoid","volume":"81","author":"Baofeng","year":"2010","journal-title":"Acta Orthop."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1007\/BF01623240","article-title":"Effects of glucocorticoids on skeletal growth in rabbits evaluated by dual-photon absorptiometry, microscopic connectivity and vertebral compressive strength","volume":"4","author":"Grardel","year":"1994","journal-title":"Osteoporos. Int."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1097\/BRS.0b013e3181b8e0ff","article-title":"Glucocorticoid induced osteopenia in cancellous bone of sheep: Validation of large animal model for spine fusion and biomaterial research","volume":"35","author":"Ding","year":"2010","journal-title":"Spine"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"59","DOI":"10.22203\/eCM.v033a05","article-title":"Recent advances in hydrogels for cartilage tissue engineering","volume":"33","author":"Vega","year":"2017","journal-title":"Eur. Cell. Mater."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1038\/s41467-018-08278-4","article-title":"BMP9 stimulates joint regeneration at digit amputation wounds in mice","volume":"10","author":"Yu","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1016\/j.devcel.2019.12.004","article-title":"Acquisition of a Unique Mesenchymal Precursor-like Blastema State Underlies Successful Adult Mammalian Digit Tip Regeneration","volume":"52","author":"Storer","year":"2020","journal-title":"Dev. Cell"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.joca.2012.11.012","article-title":"Osteoarthritis as an inflammatory disease (osteoarthritis is not osteoarthrosis!)","volume":"21","author":"Berenbaum","year":"2013","journal-title":"Osteoarthr. Cartil."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1097\/BOR.0b013e328349c2b1","article-title":"Inflammation in osteoarthritis","volume":"23","author":"Goldring","year":"2011","journal-title":"Curr. Opin. Rheumatol."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1038\/nrrheum.2010.198","article-title":"The role of the cartilage matrix in osteoarthritis","volume":"7","author":"Saxne","year":"2011","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1038\/nm.2146","article-title":"Transcriptional regulation of endochondral ossification by HIF-2alpha during skeletal growth and osteoarthritis development","volume":"16","author":"Saito","year":"2010","journal-title":"Nat. Med."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"2072","DOI":"10.1101\/gad.13.16.2072","article-title":"Indian hedgehog signaling regulates proliferation and differentiation of chondrocytes and is essential for bone formation","volume":"13","author":"Hammerschmidt","year":"1999","journal-title":"Genes Dev."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.matbio.2015.10.001","article-title":"Structural and mechanical properties of the proliferative zone of the developing murine growth plate cartilage assessed by atomic force microscopy","volume":"50","author":"Prein","year":"2016","journal-title":"Matrix Biol."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"1095","DOI":"10.1016\/j.nut.2011.03.002","article-title":"Selenium, iodine, and the relation with Kashin-Beck disease","volume":"27","author":"Yao","year":"2011","journal-title":"Nutrition"},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"748360","DOI":"10.3389\/fmolb.2021.748360","article-title":"Single-Cell Profiles of Age-Related Osteoarthritis Uncover Underlying Heterogeneity Associated With Disease Progression","volume":"8","author":"Liu","year":"2021","journal-title":"Front. Mol. Biosci."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"109117","DOI":"10.1016\/j.clim.2022.109117","article-title":"RNA-seq characterization of histamine-releasing mast cells as potential therapeutic target of osteoarthritis","volume":"244","author":"Zhao","year":"2022","journal-title":"Clin. Immunol."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"103618","DOI":"10.1016\/j.ebiom.2021.103618","article-title":"Synovial tissue from sites of joint pain in knee osteoarthritis patients exhibits a differential phenotype with distinct fibroblast subsets","volume":"72","author":"Nanus","year":"2021","journal-title":"EBioMedicine"},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"2447","DOI":"10.1038\/s41467-022-30119-8","article-title":"Dual functions of microRNA-17 in maintaining cartilage homeostasis and protection against osteoarthritis","volume":"13","author":"Zhang","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1016\/j.joca.2021.03.007","article-title":"Combining segmental bulk- and single-cell RNA-sequencing to define the chondrocyte gene expression signature in the murine knee joint","volume":"29","author":"Sunkara","year":"2021","journal-title":"Osteoarthr. Cartil."},{"key":"ref_138","doi-asserted-by":"crossref","unstructured":"Knights, A.J., Farrell, E.C., Ellis, O.M., Lammlin, L., Junginger, L.M., Rzeczycki, P.M., Bergman, R.F., Pervez, R., Cruz, M., and Knight, E. (2022). Synovial fibroblasts assume distinct functional identities and secrete R-spondin 2 in osteoarthritis. Ann. Rheum. Dis.","DOI":"10.1101\/2022.05.06.489035"},{"key":"ref_139","doi-asserted-by":"crossref","unstructured":"Sebastian, A., McCool, J.L., Hum, N.R., Murugesh, D.K., Wilson, S.P., Christiansen, B.A., and Loots, G.G. (2021). Single-Cell RNA-Seq Reveals Transcriptomic Heterogeneity and Post-Traumatic Osteoarthritis-Associated Early Molecular Changes in Mouse Articular Chondrocytes. Cells, 10.","DOI":"10.3390\/cells10061462"},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"938075","DOI":"10.3389\/fimmu.2022.938075","article-title":"Single-cell RNA-Seq reveals changes in immune landscape in post-traumatic osteoarthritis","volume":"13","author":"Sebastian","year":"2022","journal-title":"Front. Immunol."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"709178","DOI":"10.3389\/fimmu.2021.709178","article-title":"New Insights From Single-Cell Sequencing Data: Synovial Fibroblasts and Synovial Macrophages in Rheumatoid Arthritis","volume":"12","author":"Cheng","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"11876","DOI":"10.1038\/s41598-022-15293-5","article-title":"Integrated single cell and spatial transcriptomics reveal autoreactive differentiated B cells in joints of early rheumatoid arthritis","volume":"12","author":"Hardt","year":"2022","journal-title":"Sci. Rep."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"4046","DOI":"10.1038\/s41467-022-31519-6","article-title":"Single cell sequencing identifies clonally expanded synovial CD4+ TPH cells expressing GPR56 in rheumatoid arthritis","volume":"13","author":"Argyriou","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"4977","DOI":"10.1038\/s41467-021-25246-7","article-title":"Single-cell sequencing of immune cells from anticitrullinated peptide antibody positive and negative rheumatoid arthritis","volume":"12","author":"Wu","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1186\/s13073-019-0657-3","article-title":"A validated single-cell-based strategy to identify diagnostic and therapeutic targets in complex diseases","volume":"11","author":"Gawel","year":"2019","journal-title":"Genome Med."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1038\/s41584-021-00713-z","article-title":"A new immunometabolic perspective of intervertebral disc degeneration","volume":"18","author":"Francisco","year":"2022","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"45238","DOI":"10.1038\/srep45238","article-title":"Novel model of tendon regeneration reveals distinct cell mechanisms underlying regenerative and fibrotic tendon healing","volume":"7","author":"Howell","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1038\/ncprheum0700","article-title":"Tendinopathy--from basic science to treatment","volume":"4","author":"Riley","year":"2008","journal-title":"Nat. Clin. Pract. Rheumatol."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1080\/15459620590929635","article-title":"Prevalence of musculoskeletal disorders in union ironworkers","volume":"2","author":"Forde","year":"2005","journal-title":"J. Occup. Environ. Hyg."},{"key":"ref_150","doi-asserted-by":"crossref","unstructured":"Thorborg, K., Opar, D., and Shield, A. (2020). Prevention and Rehabilitation of Hamstring Injuries, Springer International Publishing.","DOI":"10.1007\/978-3-030-31638-9"},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1016\/j.berh.2006.12.004","article-title":"Muscle injuries: Optimising recovery","volume":"21","author":"Vaittinen","year":"2007","journal-title":"Best Pract. Res. Clin. Rheumatol."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.csm.2008.08.009","article-title":"Stem cells for the treatment of skeletal muscle injury","volume":"28","author":"Quintero","year":"2009","journal-title":"Clin. Sports Med."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"854","DOI":"10.1038\/nm.3918","article-title":"The central role of muscle stem cells in regenerative failure with aging","volume":"21","author":"Blau","year":"2015","journal-title":"Nat. Med."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/j.devcel.2018.06.018","article-title":"A muscle stem cell support group: Coordinated cellular responses in muscle regeneration","volume":"46","author":"Wosczyna","year":"2018","journal-title":"Dev. Cell"},{"key":"ref_155","doi-asserted-by":"crossref","unstructured":"Tabula Muris Consortium, Overall coordination, Logistical coordination, Organ collection and processing, Library preparation and sequencing, Computational data analysis, Cell type annotation, Writing group, Supplemental text writing group, and Principal investigators (2018). Single-cell transcriptomics of 20 mouse organs creates a Tabula Muris. Nature, 562, 367\u2013372.","DOI":"10.1038\/s41586-018-0590-4"},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1038\/s41598-019-57110-6","article-title":"Single-cell transcriptional profiles in human skeletal muscle","volume":"10","author":"Rubenstein","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"1062","DOI":"10.1038\/embor.2013.182","article-title":"Cellular dynamics in the muscle satellite cell niche","volume":"14","author":"Bentzinger","year":"2013","journal-title":"EMBO Rep."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1038\/s41572-021-00248-3","article-title":"Duchenne muscular dystrophy","volume":"7","author":"Duan","year":"2021","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"2025","DOI":"10.1016\/S0140-6736(19)32910-1","article-title":"Muscular dystrophies","volume":"394","author":"Mercuri","year":"2019","journal-title":"Lancet"},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"20190259","DOI":"10.1098\/rsif.2019.0259","article-title":"Biomechanical behaviours of the bone-implant interface: A review","volume":"16","author":"Gao","year":"2019","journal-title":"J. R. Soc. Interface"},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"1222","DOI":"10.1016\/j.eng.2020.02.018","article-title":"Advances in medical applications of additive manufacturing","volume":"6","author":"Li","year":"2020","journal-title":"Engineering"},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"844","DOI":"10.1016\/j.msec.2019.04.064","article-title":"Review on titanium and titanium based alloys as biomaterials for orthopaedic applications","volume":"102","author":"Kaur","year":"2019","journal-title":"Mater. Sci. Eng. C Mater. Biol. Appl."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"1000","DOI":"10.1002\/jbmr.4264","article-title":"Tmem100- and Acta2-Lineage Cells Contribute to Implant Osseointegration in a Mouse Model","volume":"36","author":"Vesprey","year":"2021","journal-title":"J. Bone Miner. Res."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1016\/j.bioactmat.2022.10.009","article-title":"Remodeling of the osteoimmune microenvironment after biomaterials implantation in murine tibia: Single-cell transcriptome analysis","volume":"22","author":"Li","year":"2023","journal-title":"Bioact. Mater."},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1038\/nmat2614","article-title":"Emerging applications of stimuli-responsive polymer materials","volume":"9","author":"Stuart","year":"2010","journal-title":"Nat. Mater."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1007\/s00586-005-1003-6","article-title":"Bioresorbable polymers: Heading for a new generation of spinal cages","volume":"15","author":"Wuisman","year":"2006","journal-title":"Eur. Spine J."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1038\/nrrheum.2012.218","article-title":"Adverse reactions to metal-on-metal implants","volume":"9","author":"Konttinen","year":"2013","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"1228","DOI":"10.1038\/s41551-021-00770-5","article-title":"Computational reconstruction of the signalling networks surrounding implanted biomaterials from single-cell transcriptomics","volume":"5","author":"Cherry","year":"2021","journal-title":"Nat. Biomed. Eng."},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"eabj5830","DOI":"10.1126\/sciadv.abj5830","article-title":"Biomaterials direct functional B cell response in a material-specific manner","volume":"7","author":"Moore","year":"2021","journal-title":"Sci. Adv."},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1016\/j.coi.2013.09.017","article-title":"Immunosequencing: Applications of immune repertoire deep sequencing","volume":"25","author":"Robins","year":"2013","journal-title":"Curr. Opin. Immunol."},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.addr.2015.03.013","article-title":"Biomaterial strategies for engineering implants for enhanced osseointegration and bone repair","volume":"94","author":"Agarwal","year":"2015","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1016\/j.bioactmat.2022.01.043","article-title":"A hydrogel spinal dural patch with potential anti-inflammatory, pain relieving and antibacterial effects","volume":"14","author":"Li","year":"2022","journal-title":"Bioact. Mater."},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1038\/s41536-021-00187-3","article-title":"Long-term repair of porcine articular cartilage using cryopreservable, clinically compatible human embryonic stem cell-derived chondrocytes","volume":"6","author":"Petrigliano","year":"2021","journal-title":"NPJ Regen. Med."},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1016\/j.cell.2007.11.019","article-title":"Induction of pluripotent stem cells from adult human fibroblasts by defined factors","volume":"131","author":"Takahashi","year":"2007","journal-title":"Cell"},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"1145","DOI":"10.1126\/science.282.5391.1145","article-title":"Embryonic stem cell lines derived from human blastocysts","volume":"282","author":"Thomson","year":"1998","journal-title":"Science"},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1038\/s41467-020-20598-y","article-title":"Single cell transcriptomic analysis of human pluripotent stem cell chondrogenesis","volume":"12","author":"Wu","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"5012","DOI":"10.1038\/s41467-021-25328-6","article-title":"Grafting of iPS cell-derived tenocytes promotes motor function recovery after Achilles tendon rupture","volume":"12","author":"Nakajima","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"950","DOI":"10.1158\/1078-0432.CCR-05-1220","article-title":"BMS-345541 targets inhibitor of kappaB kinase and induces apoptosis in melanoma: Involvement of nuclear factor kappaB and mitochondria pathways","volume":"12","author":"Yang","year":"2006","journal-title":"Clin. Cancer Res."},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"14008","DOI":"10.1038\/boneres.2014.8","article-title":"Kartogenin induces cartilage-like tissue formation in tendon-bone junction","volume":"2","author":"Zhang","year":"2014","journal-title":"Bone Res."},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"1658","DOI":"10.1093\/ibd\/izaa089","article-title":"Inflammatory Bowel Disease Through the Lens of Single-cell RNA-seq Technologies","volume":"26","author":"Corridoni","year":"2020","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"910","DOI":"10.1126\/science.aab1601","article-title":"Multiplex single cell profiling of chromatin accessibility by combinatorial cellular indexing","volume":"348","author":"Cusanovich","year":"2015","journal-title":"Science"},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1038\/nature14590","article-title":"Single-cell chromatin accessibility reveals principles of regulatory variation","volume":"523","author":"Buenrostro","year":"2015","journal-title":"Nature"},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1186\/s13059-022-02698-8","article-title":"Comprehensive benchmarking of CITE-seq versus DOGMA-seq single cell multimodal omics","volume":"23","author":"Xu","year":"2022","journal-title":"Genome Biol."},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"936","DOI":"10.1038\/nbt.3973","article-title":"Multiplexed quantification of proteins and transcripts in single cells","volume":"35","author":"Peterson","year":"2017","journal-title":"Nat. Biotechnol."},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"1380","DOI":"10.1126\/science.aau0730","article-title":"Joint profiling of chromatin accessibility and gene expression in thousands of single cells","volume":"361","author":"Cao","year":"2018","journal-title":"Science"},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"1452","DOI":"10.1038\/s41587-019-0290-0","article-title":"High-throughput sequencing of the transcriptome and chromatin accessibility in the same cell","volume":"37","author":"Chen","year":"2019","journal-title":"Nat. Biotechnol."},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"1103","DOI":"10.1016\/j.cell.2020.09.056","article-title":"Chromatin Potential Identified by Shared Single-Cell Profiling of RNA and Chromatin","volume":"183","author":"Ma","year":"2020","journal-title":"Cell"},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"1246","DOI":"10.1038\/s41587-021-00927-2","article-title":"Scalable, multimodal profiling of chromatin accessibility, gene expression and protein levels in single cells","volume":"39","author":"Mimitou","year":"2021","journal-title":"Nat. Biotechnol."},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"e63632","DOI":"10.7554\/eLife.63632","article-title":"Simultaneous trimodal single-cell measurement of transcripts, epitopes, and chromatin accessibility using TEA-seq","volume":"10","author":"Swanson","year":"2021","journal-title":"eLife"},{"key":"ref_190","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1126\/science.abg7216","article-title":"Spatial-CUT&Tag: Spatially resolved chromatin modification profiling at the cellular level","volume":"375","author":"Deng","year":"2022","journal-title":"Science"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/3\/2271\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:14:18Z","timestamp":1760120058000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/3\/2271"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1,23]]},"references-count":190,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2023,2]]}},"alternative-id":["ijms24032271"],"URL":"https:\/\/doi.org\/10.3390\/ijms24032271","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,1,23]]}}}