{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T22:11:27Z","timestamp":1794003087726,"version":"4.8.0"},"reference-count":52,"publisher":"Elsevier BV","issue":"10","license":[{"start":{"date-parts":[[2023,10,1]],"date-time":"2023-10-01T00:00:00Z","timestamp":1696118400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2023,10,1]],"date-time":"2023-10-01T00:00:00Z","timestamp":1696118400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2023,10,5]],"date-time":"2023-10-05T00:00:00Z","timestamp":1696464000000},"content-version":"vor","delay-in-days":4,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007219","name":"Natural Science Foundation of Shanghai Municipality","doi-asserted-by":"publisher","award":["22ZR1437600"],"award-info":[{"award-number":["22ZR1437600"]}],"id":[{"id":"10.13039\/100007219","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81870785"],"award-info":[{"award-number":["81870785"]}],"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":["82071134"],"award-info":[{"award-number":["82071134"]}],"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":["82370980"],"award-info":[{"award-number":["82370980"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008233","name":"School of Medicine, Shanghai Jiao Tong University","doi-asserted-by":"publisher","award":["2022ZZ01017"],"award-info":[{"award-number":["2022ZZ01017"]}],"id":[{"id":"10.13039\/501100008233","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008233","name":"School of Medicine, Shanghai Jiao Tong University","doi-asserted-by":"publisher","award":["YBKA201908"],"award-info":[{"award-number":["YBKA201908"]}],"id":[{"id":"10.13039\/501100008233","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["cell.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Heliyon"],"published-print":{"date-parts":[[2023,10]]},"DOI":"10.1016\/j.heliyon.2023.e20749","type":"journal-article","created":{"date-parts":[[2023,10,6]],"date-time":"2023-10-06T12:17:33Z","timestamp":1696594653000},"page":"e20749","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":18,"title":["Single-cell RNA sequencing reveals neurovascular-osteochondral network crosstalk during temporomandibular joint osteoarthritis: Pilot study in a human condylar cartilage"],"prefix":"10.1016","volume":"9","author":[{"given":"Dahe","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuxin","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simo","family":"Xia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weifeng","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liang","family":"Huo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pei","family":"Shen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chi","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.heliyon.2023.e20749_bib1","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/j.kjms.2018.01.004","article-title":"Functional disorders of the temporomandibular joints: internal derangement of the temporomandibular joint","volume":"34","author":"Chang","year":"2018","journal-title":"Kaohsiung J. Med. Sci."},{"key":"10.1016\/j.heliyon.2023.e20749_bib2","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.jot.2021.07.001","article-title":"Molecular signaling in temporomandibular joint osteoarthritis","volume":"32","author":"Lu","year":"2022","journal-title":"J Orthop Translat"},{"key":"10.1016\/j.heliyon.2023.e20749_bib3","doi-asserted-by":"crossref","first-page":"930","DOI":"10.1002\/j.0022-0337.2008.72.8.tb04569.x","article-title":"TMJ disorders: future innovations in diagnostics and therapeutics","volume":"72","author":"Wadhwa","year":"2008","journal-title":"J. Dent. Educ."},{"key":"10.1016\/j.heliyon.2023.e20749_bib4","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1007\/s11914-018-0447-7","article-title":"Part I: development and physiology of the temporomandibular joint","volume":"16","author":"Stocum","year":"2018","journal-title":"Curr. Osteoporos. Rep."},{"key":"10.1016\/j.heliyon.2023.e20749_bib5","doi-asserted-by":"crossref","DOI":"10.1002\/adhm.201801236","article-title":"Tissue engineering for the temporomandibular joint","volume":"8","author":"Acri","year":"2019","journal-title":"Adv. Healthcare Mater."},{"key":"10.1016\/j.heliyon.2023.e20749_bib6","doi-asserted-by":"crossref","first-page":"4902","DOI":"10.1111\/jcmm.16514","article-title":"Pathological mechanism of chondrocytes and the surrounding environment during osteoarthritis of temporomandibular joint","volume":"25","author":"Li","year":"2021","journal-title":"J. Cell Mol. Med."},{"key":"10.1016\/j.heliyon.2023.e20749_bib7","doi-asserted-by":"crossref","DOI":"10.1038\/boneres.2016.44","article-title":"Osteoarthritis: toward a comprehensive understanding of pathological mechanism","volume":"5","author":"Chen","year":"2017","journal-title":"Bone Res"},{"key":"10.1016\/j.heliyon.2023.e20749_bib8","article-title":"An update on mesenchymal stem cell-centered therapies in temporomandibular joint osteoarthritis","volume":"2021","author":"Zhao","year":"2021","journal-title":"Stem Cell. Int."},{"key":"10.1016\/j.heliyon.2023.e20749_bib9","doi-asserted-by":"crossref","DOI":"10.3389\/fbioe.2022.901749","article-title":"Interaction of neurovascular signals in the degraded condylar cartilage","volume":"10","author":"Qin","year":"2022","journal-title":"Front. Bioeng. Biotechnol."},{"key":"10.1016\/j.heliyon.2023.e20749_bib10","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1177\/0022034512441946","article-title":"Sustained inflammation induces degeneration of the temporomandibular joint","volume":"91","author":"Wang","year":"2012","journal-title":"J. Dent. Res."},{"key":"10.1016\/j.heliyon.2023.e20749_bib11","doi-asserted-by":"crossref","first-page":"666","DOI":"10.1177\/0022034515574770","article-title":"Current understanding of pathogenesis and treatment of TMJ osteoarthritis","volume":"94","author":"Wang","year":"2015","journal-title":"J. Dent. Res."},{"key":"10.1016\/j.heliyon.2023.e20749_bib12","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1038\/s41413-021-00147-z","article-title":"Subchondral bone microenvironment in osteoarthritis and pain","volume":"9","author":"Hu","year":"2021","journal-title":"Bone Res"},{"key":"10.1016\/j.heliyon.2023.e20749_bib13","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1136\/annrheumdis-2020-216942","article-title":"Horizontal fissuring at the osteochondral interface: a novel and unique pathological feature in patients with obesity-related osteoarthritis","volume":"79","author":"Chen","year":"2020","journal-title":"Ann. Rheum. Dis."},{"key":"10.1016\/j.heliyon.2023.e20749_bib14","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1038\/nrrheum.2012.80","article-title":"Mechanisms and targets of angiogenesis and nerve growth in osteoarthritis","volume":"8","author":"Mapp","year":"2012","journal-title":"Nat. Rev. Rheumatol."},{"key":"10.1016\/j.heliyon.2023.e20749_bib15","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1053\/joca.1998.0238","article-title":"Osteoarthritic cartilage loses its ability to remain avascular","volume":"7","author":"Fenwick","year":"1999","journal-title":"Osteoarthritis Cartilage"},{"key":"10.1016\/j.heliyon.2023.e20749_bib16","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1097\/BOR.0b013e3282ba5693","article-title":"Hypoxia and osteoarthritis: how chondrocytes survive hypoxic environments","volume":"19","author":"Pfander","year":"2007","journal-title":"Curr. Opin. Rheumatol."},{"key":"10.1016\/j.heliyon.2023.e20749_bib17","doi-asserted-by":"crossref","DOI":"10.1002\/advs.202003390","article-title":"Crosstalk between bone and nerves within bone","volume":"8","author":"Wan","year":"2021","journal-title":"Adv. Sci."},{"key":"10.1016\/j.heliyon.2023.e20749_bib18","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1038\/nature03875","article-title":"Common mechanisms of nerve and blood vessel wiring","volume":"436","author":"Carmeliet","year":"2005","journal-title":"Nature"},{"key":"10.1016\/j.heliyon.2023.e20749_bib19","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1002\/jor.1100130104","article-title":"Expression of type-X collagen in osteoarthritis","volume":"13","author":"Walker","year":"1995","journal-title":"J. Orthop. Res."},{"key":"10.1016\/j.heliyon.2023.e20749_bib20","article-title":"Animal models of temporomandibular joint osteoarthritis: classification and selection","volume":"13","author":"Zhao","year":"2022","journal-title":"Front. Physiol."},{"key":"10.1016\/j.heliyon.2023.e20749_bib21","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1089\/ten.tec.2020.0294","article-title":"Collagen-induced temporomandibular joint arthritis juvenile rat animal model","volume":"27","author":"Crossman","year":"2021","journal-title":"Tissue Eng. C Methods"},{"key":"10.1016\/j.heliyon.2023.e20749_bib22","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1016\/j.joca.2020.12.016","article-title":"Initiation and progression of dental-stimulated temporomandibular joints osteoarthritis","volume":"29","author":"Liu","year":"2021","journal-title":"Osteoarthritis Cartilage"},{"key":"10.1016\/j.heliyon.2023.e20749_bib23","doi-asserted-by":"crossref","first-page":"11489","DOI":"10.1111\/jcmm.15763","article-title":"TLR4 contributes to the damage of cartilage and subchondral bone in discectomy-induced TMJOA mice","volume":"24","author":"Liu","year":"2020","journal-title":"J. Cell Mol. Med."},{"key":"10.1016\/j.heliyon.2023.e20749_bib24","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1111\/nyas.14741","article-title":"Experimental functional shift-induced osteoarthritis-like changes at the TMJ and altered integrin expression in a rat model","volume":"1511","author":"Zou","year":"2022","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"10.1016\/j.heliyon.2023.e20749_bib25","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1038\/s41536-022-00265-0","article-title":"Rapid induction and long-term self-renewal of neural crest-derived ectodermal chondrogenic cells from hPSCs","volume":"7","author":"Shen","year":"2022","journal-title":"NPJ Regen Med"},{"key":"10.1016\/j.heliyon.2023.e20749_bib26","series-title":"R: A Language and Environment for Statistical Computing","author":"Team","year":"2021"},{"key":"10.1016\/j.heliyon.2023.e20749_bib27","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1038\/nbt.3192","article-title":"Spatial reconstruction of single-cell gene expression data","volume":"33","author":"Satija","year":"2015","journal-title":"Nat. Biotechnol."},{"key":"10.1016\/j.heliyon.2023.e20749_bib28","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1016\/j.cels.2019.03.003","article-title":"DoubletFinder: doublet detection in single-cell RNA sequencing data using artificial nearest neighbors","volume":"8","author":"McGinnis","year":"2019","journal-title":"Cell Syst"},{"key":"10.1016\/j.heliyon.2023.e20749_bib29","doi-asserted-by":"crossref","first-page":"1289","DOI":"10.1038\/s41592-019-0619-0","article-title":"Fast, sensitive and accurate integration of single-cell data with Harmony","volume":"16","author":"Korsunsky","year":"2019","journal-title":"Nat. Methods"},{"key":"10.1016\/j.heliyon.2023.e20749_bib30","article-title":"clusterProfiler 4.0: a universal enrichment tool for interpreting omics data","volume":"2","author":"Wu","year":"2021","journal-title":"Innovation"},{"key":"10.1016\/j.heliyon.2023.e20749_bib31","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":"H\u00e4nzelmann","year":"2013","journal-title":"BMC Bioinf."},{"key":"10.1016\/j.heliyon.2023.e20749_bib32","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1038\/nmeth.4150","article-title":"Single-cell mRNA quantification and differential analysis with Census","volume":"14","author":"Qiu","year":"2017","journal-title":"Nat. Methods"},{"key":"10.1016\/j.heliyon.2023.e20749_bib33","series-title":"Single-cell Transcriptional Diversity Is a Hallmark of Developmental Potential","author":"Gulati","year":"2019"},{"key":"10.1016\/j.heliyon.2023.e20749_bib34","doi-asserted-by":"crossref","first-page":"2498","DOI":"10.1101\/gr.1239303","article-title":"Cytoscape: a software environment for integrated models of biomolecular interaction networks","volume":"13","author":"Shannon","year":"2003","journal-title":"Genome Res."},{"key":"10.1016\/j.heliyon.2023.e20749_bib35","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/j.mehy.2018.08.023","article-title":"Cartilage degradation in osteoarthritis: a process of osteochondral remodeling resembles the endochondral ossification in growth plate?","volume":"121","author":"Xiao","year":"2018","journal-title":"Med. Hypotheses"},{"key":"10.1016\/j.heliyon.2023.e20749_bib36","doi-asserted-by":"crossref","first-page":"426","DOI":"10.7150\/thno.34126","article-title":"Type H blood vessels in bone modeling and remodeling","volume":"10","author":"Peng","year":"2020","journal-title":"Theranostics"},{"key":"10.1016\/j.heliyon.2023.e20749_bib37","article-title":"CTGF as a multifunctional molecule for cartilage and a potential drug for osteoarthritis","volume":"13","author":"Yang","year":"2022","journal-title":"Front. Endocrinol."},{"key":"10.1016\/j.heliyon.2023.e20749_bib38","article-title":"Identification and functional characterization of imbalanced osteoarthritis associated fibronectin splice variants","author":"van Hoolwerff","year":"2022","journal-title":"Rheumatology"},{"key":"10.1016\/j.heliyon.2023.e20749_bib39","doi-asserted-by":"crossref","DOI":"10.1126\/scitranslmed.abb3946","article-title":"Targeting cartilage EGFR pathway for osteoarthritis treatment","volume":"13","author":"Wei","year":"2021","journal-title":"Sci. Transl. Med."},{"key":"10.1016\/j.heliyon.2023.e20749_bib40","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1016\/j.matbio.2013.01.004","article-title":"Synovial perlecan is required for osteophyte formation in knee osteoarthritis","volume":"32","author":"Kaneko","year":"2013","journal-title":"Matrix Biol."},{"key":"10.1016\/j.heliyon.2023.e20749_bib41","doi-asserted-by":"crossref","first-page":"4265","DOI":"10.7150\/thno.35914","article-title":"COL4A2 in the tissue-specific extracellular matrix plays important role on osteogenic differentiation of periodontal ligament stem cells","volume":"9","author":"Wen","year":"2019","journal-title":"Theranostics"},{"key":"10.1016\/j.heliyon.2023.e20749_bib42","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1111\/j.1365-2842.2012.02332.x","article-title":"Differential expression of IGF1, IGFR1 and IGFBP3 in mandibular condylar cartilage between male and female rats applied with malocclusion","volume":"39","author":"Yu","year":"2012","journal-title":"J. Oral Rehabil."},{"key":"10.1016\/j.heliyon.2023.e20749_bib43","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1016\/j.joca.2020.02.027","article-title":"The PI3K\/AKT\/mTOR signaling pathway in osteoarthritis: a narrative review","volume":"28","author":"Sun","year":"2020","journal-title":"Osteoarthritis Cartilage"},{"key":"10.1016\/j.heliyon.2023.e20749_bib44","doi-asserted-by":"crossref","first-page":"1062","DOI":"10.1016\/j.cell.2009.03.048","article-title":"Autophagy suppresses tumorigenesis through elimination of p62","volume":"137","author":"Mathew","year":"2009","journal-title":"Cell"},{"key":"10.1016\/j.heliyon.2023.e20749_bib45","first-page":"248","article-title":"[Current views on the pathogenesis of osteoarthritis]","volume":"75","author":"\u0141apaj","year":"2010","journal-title":"Chir. Narzadow Ruchu Ortop. Pol."},{"key":"10.1016\/j.heliyon.2023.e20749_bib46","doi-asserted-by":"crossref","first-page":"909","DOI":"10.1002\/jbmr.3388","article-title":"Positive-feedback regulation of subchondral H-type vessel formation by chondrocyte promotes osteoarthritis development in mice","volume":"33","author":"Lu","year":"2018","journal-title":"J. Bone Miner. Res."},{"key":"10.1016\/j.heliyon.2023.e20749_bib47","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1016\/j.joca.2013.11.015","article-title":"Depletion of gangliosides enhances cartilage degradation in mice","volume":"22","author":"Sasazawa","year":"2014","journal-title":"Osteoarthritis Cartilage"},{"key":"10.1016\/j.heliyon.2023.e20749_bib48","doi-asserted-by":"crossref","first-page":"1227","DOI":"10.1136\/ard.2009.120857","article-title":"Serum branched-chain amino acid to histidine ratio: a novel metabolomic biomarker of knee osteoarthritis","volume":"69","author":"Zhai","year":"2010","journal-title":"Ann. Rheum. Dis."},{"key":"10.1016\/j.heliyon.2023.e20749_bib49","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1007\/BF00541315","article-title":"Serum and synovial fluid histidine: a comparison in rheumatoid arthritis and osteoarthritis","volume":"6","author":"Sitton","year":"1986","journal-title":"Rheumatol. Int."},{"key":"10.1016\/j.heliyon.2023.e20749_bib50","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1016\/j.cca.2020.07.010","article-title":"Insight into osteoarthritis through integrative analysis of metabolomics and transcriptomics","volume":"510","author":"Huang","year":"2020","journal-title":"Clin. Chim. Acta"},{"key":"10.1016\/j.heliyon.2023.e20749_bib51","doi-asserted-by":"crossref","first-page":"1132","DOI":"10.1016\/j.joca.2023.04.007","article-title":"Serum tryptophan metabolites are associated with erosive hand osteoarthritis and pain: results from the DIGICOD cohort","volume":"31","author":"Binvignat","year":"2023","journal-title":"Osteoarthritis Cartilage"},{"key":"10.1016\/j.heliyon.2023.e20749_bib52","doi-asserted-by":"crossref","first-page":"1389","DOI":"10.1016\/j.joca.2021.07.003","article-title":"Tyrosine kinases regulate chondrocyte hypertrophy: promising drug targets for Osteoarthritis","volume":"29","author":"Ferrao Blanco","year":"2021","journal-title":"Osteoarthritis Cartilage"}],"container-title":["Heliyon"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2405844023079574?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2405844023079574?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T08:27:23Z","timestamp":1790756843000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S2405844023079574"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,10]]},"references-count":52,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2023,10]]}},"alternative-id":["S2405844023079574"],"URL":"https:\/\/doi.org\/10.1016\/j.heliyon.2023.e20749","relation":{},"ISSN":["2405-8440"],"issn-type":[{"value":"2405-8440","type":"print"}],"subject":[],"published":{"date-parts":[[2023,10]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Single-cell RNA sequencing reveals neurovascular-osteochondral network crosstalk during temporomandibular joint osteoarthritis: Pilot study in a human condylar cartilage","name":"articletitle","label":"Article Title"},{"value":"Heliyon","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.heliyon.2023.e20749","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2023 The Authors. Published by Elsevier Ltd.","name":"copyright","label":"Copyright"}],"article-number":"e20749"}}