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Any abnormal regulation in the bone development processes causes skeletal system-related problems. To some extent, the avascularity of cartilage and bone makes drug delivery more challenging than that of soft tissues. Recent studies have implemented many novel bone-targeting approaches to overcome drawbacks. However, none of these strategies fully corrects skeletal dysfunction, particularly in growth plate-related ones. Although direct recombinant enzymes (e.g., Vimizim for Morquio, Cerezyme for Gaucher, Elaprase for Hunter, Mepsevii for Sly diseases) or hormone infusions (estrogen for osteoporosis and osteoarthritis), traditional gene delivery (e.g., direct infusion of viral or non-viral vectors with no modifications on capsid, envelope, or nanoparticles), and cell therapy strategies (healthy bone marrow or hematopoietic stem cell transplantation) partially improve bone lesions, novel delivery methods must be addressed regarding target specificity, less immunogenicity, and duration in circulation. In addition to improvements in bone delivery, potential regulation of bone development mechanisms involving receptor-regulated pathways has also been utilized. Targeted drug delivery using organic and inorganic compounds is a promising approach in mostly preclinical settings and future clinical translation. This review comprehensively summarizes the current bone-targeting strategies based on bone structure and remodeling concepts while emphasizing potential approaches for future bone-targeting systems.<\/jats:p>","DOI":"10.3390\/ijms25158339","type":"journal-article","created":{"date-parts":[[2024,7,31]],"date-time":"2024-07-31T08:02:27Z","timestamp":1722412947000},"page":"8339","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Potential Targeting Mechanisms for Bone-Directed Therapies"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0379-8076","authenticated-orcid":false,"given":"Betul","family":"Celik","sequence":"first","affiliation":[{"name":"Department of Biological Sciences, University of Delaware, Newark, DE 19716, USA"},{"name":"Nemours Children\u2019s Health, 1600 Rockland Rd., Wilmington, DE 19803, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5956-1986","authenticated-orcid":false,"given":"Andr\u00e9s Felipe","family":"Leal","sequence":"additional","affiliation":[{"name":"Nemours Children\u2019s Health, 1600 Rockland Rd., Wilmington, DE 19803, USA"},{"name":"Institute for the Study of Inborn Errors of Metabolism, Faculty of Science, Pontificia Universidad Javeriana, Bogot\u00e1 110231, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0673-2160","authenticated-orcid":false,"given":"Shunji","family":"Tomatsu","sequence":"additional","affiliation":[{"name":"Nemours Children\u2019s Health, 1600 Rockland Rd., Wilmington, DE 19803, USA"},{"name":"Department of Pediatrics, Graduate School of Medicine, Gifu University, Gifu 501-1193, Japan"},{"name":"Department of Pediatrics, Thomas Jefferson University, Philadelphia, PA 19144, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,7,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3697","DOI":"10.7150\/ijms.61080","article-title":"The Role of the Immune Microenvironment in Bone Regeneration","volume":"18","author":"Yang","year":"2021","journal-title":"Int. J. Med. Sci."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1152\/physiol.00061.2014","article-title":"Physiological Bone Remodeling: Systemic Regulation and Growth Factor Involvement","volume":"31","author":"Siddiqui","year":"2016","journal-title":"Physiology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2409","DOI":"10.1080\/15548627.2023.2186112","article-title":"The Role of Autophagy in Bone Metabolism and Clinical Significance","volume":"19","author":"Wang","year":"2023","journal-title":"Autophagy"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Sawamoto, K., Gonz\u00e1lez, J.V.\u00c1., Piechnik, M., Otero, F.J., Couce, M.L., Suzuki, Y., and Tomatsu, S. (2020). Mucopolysaccharidosis IVA: Diagnosis, Treatment, and Management. Int. J. Mol. 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Med."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Stapleton, M., Sawamoto, K., Alm\u00e9ciga-D\u00edaz, C.J., Mackenzie, W.G., Mason, R.W., Orii, T., and Tomatsu, S. (2017). Development of Bone Targeting Drugs. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18071345"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1186\/s13023-019-1074-9","article-title":"Recommendations for the Management of MPS IVA: Systematic Evidence- and Consensus-Based Guidance","volume":"14","author":"Akyol","year":"2019","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Concolino, D., Deodato, F., and Parini, R. (2018). Enzyme Replacement Therapy: Efficacy and Limitations. Ital. J. Pediatr., 44.","DOI":"10.1186\/s13052-018-0562-1"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Leal, A.F., Alm\u00e9ciga-D\u00edaz, C.J., and Tomatsu, S. (2023). Mucopolysaccharidosis IVA: Current Disease Models and Drawbacks. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms242216148"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1016\/j.ymgme.2014.12.001","article-title":"Therapies for the Bone in Mucopolysaccharidoses","volume":"114","author":"Tomatsu","year":"2015","journal-title":"Mol. Genet. Metab."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1038\/s41390-018-0095-8","article-title":"Tailoring the AAV2 Capsid Vector for Bone-Targeting","volume":"84","author":"Barrera","year":"2018","journal-title":"Pediatr. Res."},{"key":"ref_14","first-page":"189","article-title":"Chemical and Biochemical Basis of Cell-Bone Matrix Interaction in Health and Disease","volume":"3","author":"Feng","year":"2009","journal-title":"Curr. Chem. Biol."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Viggers, R., Al-Mashhadi, Z., Starup-Linde, J., and Vestergaard, P. (2022). The Efficacy of Alendronate Versus Denosumab on Major Osteoporotic Fracture Risk in Elderly Patients With Diabetes Mellitus: A Danish Retrospective Cohort Study. Front. Endocrinol., 12.","DOI":"10.3389\/fendo.2021.826997"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1949","DOI":"10.1093\/ajhp\/zxaa285","article-title":"Romosozumab: A First-in-Class Sclerostin Inhibitor for Osteoporosis","volume":"77","author":"Prather","year":"2020","journal-title":"Am. J. Health-Syst. Pharm."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1080","DOI":"10.1016\/S0140-6736(21)02646-5","article-title":"Drug Therapy for Osteoporosis in Older Adults","volume":"399","author":"Reid","year":"2022","journal-title":"Lancet"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/B978-0-08-055294-1.00068-4","article-title":"Bone as a Material","volume":"Volume 2","author":"McNamara","year":"2011","journal-title":"Comprehensive Biomaterials"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1385\/IR:31:3:219","article-title":"Discoidin Domain Receptor 1: A New Class of Receptor Regulating Leukocyte-Collagen Interaction","volume":"31","author":"Yoshimura","year":"2005","journal-title":"Immunol. Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1108","DOI":"10.1016\/j.cellsig.2006.02.012","article-title":"Sensing Extracellular Matrix: An Update on Discoidin Domain Receptor Function","volume":"18","author":"Vogel","year":"2006","journal-title":"Cell Signal"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Chen, L., Kong, X., Fang, Y., Paunikar, S., Wang, X., Brown, J.A.L., Bourke, E., Li, X., and Wang, J. (2021). Recent Advances in the Role of Discoidin Domain Receptor Tyrosine Kinase 1 and Discoidin Domain Receptor Tyrosine Kinase 2 in Breast and Ovarian Cancer. Front. Cell Dev. Biol., 9.","DOI":"10.3389\/fcell.2021.747314"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1016\/j.matbio.2006.05.006","article-title":"The Discoidin Domain Receptor DDR2 Is a Receptor for Type X Collagen","volume":"25","author":"Leitinger","year":"2006","journal-title":"Matrix Biol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"5767","DOI":"10.1096\/fj.201901852RR","article-title":"Discoidin Domain Receptor 1 Regulates Endochondral Ossification through Terminal Differentiation of Chondrocytes","volume":"34","author":"Chou","year":"2020","journal-title":"FASEB J."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1038\/s41413-021-00182-w","article-title":"The Collagen Receptor, Discoidin Domain Receptor 2, Functions in Gli1-Positive Skeletal Progenitors and Chondrocytes to Control Bone Development","volume":"10","author":"Mohamed","year":"2022","journal-title":"Bone Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1186\/s13287-018-0798-0","article-title":"Extracellular Matrix Stiffness Controls Osteogenic Differentiation of Mesenchymal Stem Cells Mediated by Integrin A5","volume":"9","author":"Sun","year":"2018","journal-title":"Stem Cell Res. Ther."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1186\/s12964-023-01252-8","article-title":"Extracellular Matrix-Induced Signaling Pathways in Mesenchymal Stem\/Stromal Cells","volume":"21","author":"Novoseletskaya","year":"2023","journal-title":"Cell Commun. Signal."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"C685","DOI":"10.1152\/ajpcell.00398.2014","article-title":"Suppression of Discoidin Domain Receptor 1 Expression Enhances the Chondrogenesis of Adipose-Derived Stem Cells","volume":"308","author":"Wu","year":"2015","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_28","first-page":"195","article-title":"The Expression of Two Collagen Receptor Subfamilies, Integrins and Discoidin Domains during Osteogenic and Chondrogenic Differentiation of Human Mesenehymal Stem Cells","volume":"32","author":"Xue","year":"2021","journal-title":"Biomed. Mater. Eng."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"670","DOI":"10.1007\/s00774-020-01108-y","article-title":"DDR2, a Discoidin Domain Receptor, Is a Marker of Periosteal Osteoblast and Osteoblast Progenitors","volume":"38","author":"Yang","year":"2020","journal-title":"J. Bone Miner. Metab."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Rintz, E., W\u0119grzyn, G., Fujii, T., and Tomatsu, S. (2022). Molecular Mechanism of Induction of Bone Growth by the C-Type Natriuretic Peptide. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23115916"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Mariadoss, A.V.A., and Wang, C.-Z. (2023). Exploring the Cellular and Molecular Mechanism of Discoidin Domain Receptors (DDR1 and DDR2) in Bone Formation, Regeneration, and Its Associated Disease Conditions. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241914895"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1007\/s00044-020-02694-2","article-title":"DDR1 and DDR2: A Review on Signaling Pathway and Small Molecule Inhibitors as an Anticancer Agent","volume":"30","author":"Matada","year":"2021","journal-title":"Med. Chem. Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1497","DOI":"10.1007\/s12094-021-02552-6","article-title":"Complex Roles of Discoidin Domain Receptor Tyrosine Kinases in Cancer","volume":"23","author":"Mehta","year":"2021","journal-title":"Clin. Transl. Oncol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1007\/978-1-0716-2946-8_1","article-title":"Detection of Glycosaminoglycans in Biological Specimens","volume":"2619","author":"Khan","year":"2023","journal-title":"Methods Mol. Biol."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Carvalho, M.S., Cabral, J.M.S., da Silva, C.L., and Vashishth, D. (2021). Bone Matrix Non-Collagenous Proteins in Tissue Engineering: Creating New Bone by Mimicking the Extracellular Matrix. Polymers, 13.","DOI":"10.3390\/polym13071095"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"8193","DOI":"10.1021\/acs.chemrev.6b00010","article-title":"Chemical Synthesis of Glycosaminoglycans","volume":"116","author":"Mende","year":"2016","journal-title":"Chem. Rev."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"3915","DOI":"10.1016\/j.biomaterials.2003.10.022","article-title":"The Effect of Surface Charge on Hydroxyapatite Nucleation","volume":"25","author":"Zhu","year":"2004","journal-title":"Biomaterials"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1002\/jbm.a.35143","article-title":"Use of a Chondroitin Sulfate Bioadhesive to Enhance Integration of Bioglass Particles for Repairing Critical-Size Bone Defects","volume":"103","author":"Yang","year":"2015","journal-title":"J. Biomed. Mater. Res. A"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"4023","DOI":"10.1016\/j.biomaterials.2004.09.063","article-title":"Collagen\u2013Chondroitin Sulfate-Based PLLA\u2013SAIB-Coated RhBMP-2 Delivery System for Bone Repair","volume":"26","author":"Keskin","year":"2005","journal-title":"Biomaterials"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Fujioka-Kobayashi, M., Schaller, B., Kobayashi, E., Hernandez, M., Zhang, Y., and Miron, R. (2016). Hyaluronic Acid Gel-Based Scaffolds as Potential Carrier for Growth Factors: An In Vitro Bioassay on Its Osteogenic Potential. J. Clin. Med., 5.","DOI":"10.3390\/jcm5120112"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1016\/j.ijbiomac.2014.08.029","article-title":"Keratan Sulfate: An up-to-Date Review","volume":"72","author":"Pomin","year":"2015","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1038\/s10038-019-0604-6","article-title":"Effect of Enzyme Replacement Therapy on the Growth of Patients with Morquio A","volume":"64","author":"Doherty","year":"2019","journal-title":"J. Hum. Genet."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/j.ymgme.2014.05.013","article-title":"Enzyme Replacement Therapy in Newborn Mucopolysaccharidosis IVA Mice: Early Treatment Rescues Bone Lesions?","volume":"114","author":"Tomatsu","year":"2015","journal-title":"Mol. Genet. Metab."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Coulson-Thomas, Y.M., Coulson-Thomas, V.J., Norton, A.L., Gesteira, T.F., Cavalheiro, R.P., Meneghetti, M.C.Z., Martins, J.R., Dixon, R.A., and Nader, H.B. (2015). The Identification of Proteoglycans and Glycosaminoglycans in Archaeological Human Bones and Teeth. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0131105"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2388","DOI":"10.1021\/bm0603746","article-title":"Fibrillogenesis of Collagen Types I, II, and III with Small Leucine-Rich Proteoglycans Decorin and Biglycan","volume":"7","author":"Douglas","year":"2006","journal-title":"Biomacromolecules"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Diehl, V., Huber, L.S., Trebicka, J., Wygrecka, M., Iozzo, R.V., and Schaefer, L. (2021). The Role of Decorin and Biglycan Signaling in Tumorigenesis. Front. Oncol., 11.","DOI":"10.3389\/fonc.2021.801801"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Ago, Y., Rintz, E., Musini, K., Ma, Z., and Tomatsu, S. (2024). Molecular Mechanisms in Pathophysiology of Mucopolysaccharidosis and Prospects for Innovative Therapy. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25021113"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1002\/jbm.a.31501","article-title":"Influence of Collagen-fibril-based Coatings Containing Decorin and Biglycan on Osteoblast Behavior","volume":"84A","author":"Douglas","year":"2008","journal-title":"J. Biomed. Mater. Res. A"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"401","DOI":"10.3109\/03008207.2010.546536","article-title":"Keratocan Is Expressed by Osteoblasts and Can Modulate Osteogenic Differentiation","volume":"52","author":"Igwe","year":"2011","journal-title":"Connect. Tissue Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1042\/BJ20090542","article-title":"Asporin Competes with Decorin for Collagen Binding, Binds Calcium and Promotes Osteoblast Collagen Mineralization","volume":"423","author":"Kalamajski","year":"2009","journal-title":"Biochem. J."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Zhao, F., Bai, Y., Xiang, X., and Pang, X. (2023). The Role of Fibromodulin in Inflammatory Responses and Diseases Associated with Inflammation. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1191787"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1002\/jcb.1115","article-title":"Fibromodulin Is Expressed by Both Chondrocytes and Osteoblasts during Fetal Bone Development","volume":"82","author":"Gori","year":"2001","journal-title":"J. Cell Biochem."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.matbio.2015.02.003","article-title":"Proteoglycan Form and Function: A Comprehensive Nomenclature of Proteoglycans","volume":"42","author":"Iozzo","year":"2015","journal-title":"Matrix Biol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"2911","DOI":"10.1083\/jcb.201605119","article-title":"Glypican-6 Promotes the Growth of Developing Long Bones by Stimulating Hedgehog Signaling","volume":"216","author":"Capurro","year":"2017","journal-title":"J. Cell Biol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"963","DOI":"10.1369\/0022155412456380","article-title":"Biglycan","volume":"60","author":"Nastase","year":"2012","journal-title":"J. Histochem. Cytochem."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Lin, X., Patil, S., Gao, Y.-G., and Qian, A. (2020). The Bone Extracellular Matrix in Bone Formation and Regeneration. Front. Pharmacol., 11.","DOI":"10.3389\/fphar.2020.00757"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"12724","DOI":"10.1021\/acsomega.1c07225","article-title":"Alkaline Phosphatase Activity of Serum Affects Osteogenic Differentiation Cultures","volume":"7","author":"Ansari","year":"2022","journal-title":"ACS Omega"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"144855","DOI":"10.1016\/j.gene.2020.144855","article-title":"Alkaline Phosphatase: Structure, Expression and Its Function in Bone Mineralization","volume":"754","author":"Vimalraj","year":"2020","journal-title":"Gene"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"9043","DOI":"10.1039\/D0TB01777A","article-title":"Consecutive Dephosphorylation by Alkaline Phosphatase-Directed in Situ Formation of Porous Hydrogels of SF with Nanocrystalline Calcium Phosphate Ceramics for Bone Regeneration","volume":"8","author":"Li","year":"2020","journal-title":"J. Mater. Chem. B"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1835","DOI":"10.1002\/jbmr.4382","article-title":"Gene Therapy Using Adeno-Associated Virus Serotype 8 Encoding TNAP-D 10 Improves the Skeletal and Dentoalveolar Phenotypes in Alpl-\/- Mice","volume":"36","author":"Kinoshita","year":"2021","journal-title":"J. Bone Miner. Res."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1016\/j.ymgme.2019.05.014","article-title":"Genetic Correction of Induced Pluripotent Stem Cells Mediated by Transcription Activator-like Effector Nucleases Targeting ALPL Recovers Enzyme Activity and Calcification in Vitro","volume":"127","author":"Nakano","year":"2019","journal-title":"Mol. Genet. Metab."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"116778","DOI":"10.1016\/j.bone.2023.116778","article-title":"Asfotase Alfa Improved Skeletal Mineralization and Fracture Healing in a Child with MCAHS","volume":"172","author":"Kang","year":"2023","journal-title":"Bone"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"915","DOI":"10.1172\/JCI7039","article-title":"Osteopenia and Decreased Bone Formation in Osteonectin-Deficient Mice","volume":"105","author":"Delany","year":"2000","journal-title":"J. Clin. Investig."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1186\/s13018-023-04250-1","article-title":"Osteonectin Bidirectionally Regulates Osteoblast Mineralization","volume":"18","author":"Zhu","year":"2023","journal-title":"J. Orthop. Surg. Res."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1186\/s13018-021-02860-1","article-title":"Discoidin Domain Receptor 2 Activation of P38 Mitogen-Activated Protein Kinase as an Important Pathway for Osteonectin-Regulating Osteoblast Mineralization","volume":"16","author":"Zhu","year":"2021","journal-title":"J. Orthop. Surg. Res."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"2098","DOI":"10.1002\/jbmr.4336","article-title":"Discoidin Receptor 2 Controls Bone Formation and Marrow Adipogenesis","volume":"36","author":"Ge","year":"2020","journal-title":"J. Bone Miner. Res."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"7507","DOI":"10.1038\/s41598-020-64558-4","article-title":"Tetranectin, a Potential Novel Diagnostic Biomarker of Heart Failure, Is Expressed within the Myocardium and Associates with Cardiac Fibrosis","volume":"10","author":"McDonald","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/j.bone.2018.04.016","article-title":"Temporary Inhibition of the Plasminogen Activator Inhibits Periosteal Chondrogenesis and Promotes Periosteal Osteogenesis during Appendicular Bone Fracture Healing","volume":"112","author":"Bravo","year":"2018","journal-title":"Bone"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"C980","DOI":"10.1152\/ajpcell.00383.2020","article-title":"Thrombospondins in Bone Remodeling and Metastatic Bone Disease","volume":"319","author":"Carminati","year":"2020","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Cheng, Z., Jin, Y., Li, J., Shi, G., Yu, L., Shao, B., Tian, J., Du, Y., and Yuan, Z. (2023). Fibronectin-Targeting and Metalloproteinase-Activatable Smart Imaging Probe for Fluorescence Imaging and Image-Guided Surgery of Breast Cancer. J. Nanobiotechnol., 21.","DOI":"10.1186\/s12951-023-01868-5"},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Speziale, P., Arciola, C.R., and Pietrocola, G. (2019). Fibronectin and Its Role in Human Infective Diseases. Cells, 8.","DOI":"10.3390\/cells8121516"},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Alford, A.I., and Hankenson, K.D. (2023). Thrombospondins Modulate Cell Function and Tissue Structure in the Skeleton. Semin. Cell Dev. Biol.","DOI":"10.1016\/j.semcdb.2023.06.011"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"4548","DOI":"10.1210\/en.2013-1587","article-title":"Thrombospondin 1 Mediates High-Fat Diet-Induced Muscle Fibrosis and Insulin Resistance in Male Mice","volume":"154","author":"Inoue","year":"2013","journal-title":"Endocrinology"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"2604","DOI":"10.1089\/ten.tea.2013.0457","article-title":"Three-Dimensional Culture and Transforming Growth Factor Beta3 Synergistically Promote Tenogenic Differentiation of Equine Embryo-Derived Stem Cells","volume":"20","author":"Barsby","year":"2014","journal-title":"Tissue Eng. Part A"},{"key":"ref_75","first-page":"300","article-title":"Thrombospondin-4 in Tissue Remodeling","volume":"75\u201376","author":"Plow","year":"2019","journal-title":"Matrix Biol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.matbio.2014.02.003","article-title":"Control of Organization and Function of Muscle and Tendon by Thrombospondin-4","volume":"37","author":"Frolova","year":"2014","journal-title":"Matrix Biol."},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Liu, J., Pan, D., Huang, X., Wang, S., Chen, H., Zhu, Y.Z., and Ye, L. (2023). Targeting Collagen in Tumor Extracellular Matrix as a Novel Targeted Strategy in Cancer Immunotherapy. Front. Oncol., 13.","DOI":"10.3389\/fonc.2023.1225483"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1042\/BJ20052027","article-title":"Collagen Binding by the Mannose Receptor Mediated through the Fibronectin Type II Domain","volume":"395","author":"Napper","year":"2006","journal-title":"Biochem. J."},{"key":"ref_79","first-page":"4420","article-title":"Fibronectin Matrix Assembly Is Essential for Cell Condensation during Chondrogenesis","volume":"127","author":"Singh","year":"2014","journal-title":"J. Cell Sci."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1038\/cdd.2017.153","article-title":"A Vitronectin-Derived Peptide Reverses Ovariectomy-Induced Bone Loss via Regulation of Osteoblast and Osteoclast Differentiation","volume":"25","author":"Min","year":"2018","journal-title":"Cell Death Differ."},{"key":"ref_81","first-page":"24","article-title":"Adhesion to Vitronectin and Collagen I Promotes Osteogenic Differentiation of Human Mesenchymal Stem Cells","volume":"2004","author":"Salasznyk","year":"2004","journal-title":"J. Biomed. Biotechnol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.matbio.2014.11.005","article-title":"Osteopontin Binding to the Alpha 4 Integrin Requires Highest Affinity Integrin Conformation, but Is Independent of Post-Translational Modifications of Osteopontin","volume":"41","author":"Hui","year":"2015","journal-title":"Matrix Biol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"9175","DOI":"10.1074\/jbc.M109028200","article-title":"Tumor-Derived Osteopontin Is Soluble, Not Matrix Associated","volume":"277","author":"Rittling","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_84","doi-asserted-by":"crossref","unstructured":"Bai, R.-J., Li, Y.-S., and Zhang, F.-J. (2022). Osteopontin, a Bridge Links Osteoarthritis and Osteoporosis. Front. Endocrinol., 13.","DOI":"10.3389\/fendo.2022.1012508"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"2362","DOI":"10.1002\/art.24705","article-title":"Accelerated Development of Aging-associated and Instability-induced Osteoarthritis in Osteopontin-deficient Mice","volume":"60","author":"Matsui","year":"2009","journal-title":"Arthritis Rheum."},{"key":"ref_86","first-page":"3889","article-title":"Osteopontin Can Decrease the Cartilage Cellular Inflammatory Reaction Induced by LPS","volume":"8","author":"Li","year":"2015","journal-title":"Int. J. Clin. Exp. Med."},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Doyle, M.E., Dalgarno, K., Masoero, E., and Ferreira, A.M. (2023). Advances in Biomimetic Collagen Mineralisation and Future Approaches to Bone Tissue Engineering. Biopolymers, 114.","DOI":"10.1002\/bip.23527"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"11649","DOI":"10.1074\/jbc.M309296200","article-title":"Dentin Matrix Protein 1 Immobilized on Type I Collagen Fibrils Facilitates Apatite Deposition in Vitro","volume":"279","author":"He","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"303","DOI":"10.3390\/endocrines3020025","article-title":"Pathogenesis of FGF23-Related Hypophosphatemic Diseases Including X-Linked Hypophosphatemia","volume":"3","author":"Nakanishi","year":"2022","journal-title":"Endocrines"},{"key":"ref_90","unstructured":"(2024, April 19). Food and Drug Administration (FDA) FDA Approves First Therapy for Rare Inherited Form of Rickets, x-Linked Hypophosphatemia, Available online: https:\/\/www.fda.gov\/news-events\/press-announcements\/fda-approves-first-therapy-rare-inherited-form-rickets-x-linked-hypophosphatemia."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1038\/84848","article-title":"Dentinogenesis Imperfecta 1 with or without Progressive Hearing Loss Is Associated with Distinct Mutations in DSPP","volume":"27","author":"Xiao","year":"2001","journal-title":"Nat. Genet."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1016\/j.matbio.2009.03.006","article-title":"Dentin Sialoprotein and Dentin Phosphoprotein Have Distinct Roles in Dentin Mineralization","volume":"28","author":"Suzuki","year":"2009","journal-title":"Matrix Biol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.bcp.2017.02.001","article-title":"Osteocalcin and Its Endocrine Functions","volume":"132","author":"Mizokami","year":"2017","journal-title":"Biochem. Pharmacol."},{"key":"ref_94","doi-asserted-by":"crossref","unstructured":"Kapoor, K., Pi, M., Nishimoto, S.K., Quarles, L.D., Baudry, J., and Smith, J.C. (2021). The Carboxylation Status of Osteocalcin Has Important Consequences for Its Structure and Dynamics. Biochim. Et Biophys. Acta (BBA) General. Subj., 1865.","DOI":"10.1016\/j.bbagen.2020.129809"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1055\/s-0034-1368709","article-title":"Carboxylated and Uncarboxylated Forms of Osteocalcin Directly Modulate the Glucose Transport System and Inflammation in Adipocytes","volume":"46","author":"Hill","year":"2014","journal-title":"Horm. Metab. Res."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"7496","DOI":"10.1002\/jcp.29653","article-title":"Loss and Rescue of Osteocalcin and Osteopontin Modulate Osteogenic and Angiogenic Features of Mesenchymal Stem\/Stromal Cells","volume":"235","author":"Carvalho","year":"2020","journal-title":"J. Cell Physiol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"1647","DOI":"10.2174\/0929867325666180716104159","article-title":"The Role of Matrix Gla Protein (MGP) in Vascular Calcification","volume":"27","author":"Svanberg","year":"2020","journal-title":"Curr. Med. Chem."},{"key":"ref_98","doi-asserted-by":"crossref","unstructured":"Zhang, Y., Zhao, L., Wang, N., Li, J., He, F., Li, X., and Wu, S. (2019). Unexpected Role of Matrix Gla Protein in Osteoclasts: Inhibiting Osteoclast Differentiation and Bone Resorption. Mol. Cell Biol., 39.","DOI":"10.1128\/MCB.00012-19"},{"key":"ref_99","doi-asserted-by":"crossref","unstructured":"Gao, Y., Liu, S., Huang, J., Guo, W., Chen, J., Zhang, L., Zhao, B., Peng, J., Wang, A., and Wang, Y. (2014). The ECM-Cell Interaction of Cartilage Extracellular Matrix on Chondrocytes. Biomed. Res. Int., 2014.","DOI":"10.1155\/2014\/648459"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1053\/joca.1999.0277","article-title":"Integrin Expression by Primary and Immortalized Human Chondrocytes: Evidence of a Differential Role for Alpha1beta1 and Alpha2beta1 Integrins in Mediating Chondrocyte Adhesion to Types II and VI Collagen","volume":"8","author":"Loeser","year":"2000","journal-title":"Osteoarthr. Cartil."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"1795","DOI":"10.1016\/j.joca.2016.05.013","article-title":"Integrin A1\u03b21 Protects against Signs of Post-Traumatic Osteoarthritis in the Female Murine Knee Partially via Regulation of Epidermal Growth Factor Receptor Signalling","volume":"24","author":"Shin","year":"2016","journal-title":"Osteoarthr. Cartil."},{"key":"ref_102","doi-asserted-by":"crossref","unstructured":"Hu, T., Zhang, Z., Deng, C., Ma, X., and Liu, X. (2022). Effects of \u03922 Integrins on Osteoclasts, Macrophages, Chondrocytes, and Synovial Fibroblasts in Osteoarthritis. Biomolecules, 12.","DOI":"10.3390\/biom12111653"},{"key":"ref_103","doi-asserted-by":"crossref","unstructured":"Song, E.K., Jeon, J., Jang, D.G., Kim, H.E., Sim, H.J., Kwon, K.Y., Medina-Ruiz, S., Jang, H.-J., Lee, A.R., and Rho, J.G. (2018). ITGBL1 Modulates Integrin Activity to Promote Cartilage Formation and Protect against Arthritis. Sci. Transl. Med., 10.","DOI":"10.1126\/scitranslmed.aam7486"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"1706","DOI":"10.1038\/s41467-021-21948-0","article-title":"Mechanical Stress Determines the Configuration of TGF\u03b2 Activation in Articular Cartilage","volume":"12","author":"Zhen","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1152\/physrev.00013.2022","article-title":"Ion Channels and Channelopathies in Glomeruli","volume":"103","author":"Staruschenko","year":"2023","journal-title":"Physiol. Rev."},{"key":"ref_106","doi-asserted-by":"crossref","unstructured":"Guardiani, C., Cecconi, F., Chiodo, L., Cottone, G., Malgaretti, P., Maragliano, L., Barabash, M.L., Camisasca, G., Ceccarelli, M., and Corry, B. (2022). Computational Methods and Theory for Ion Channel Research. Adv. Phys. X, 7.","DOI":"10.1080\/23746149.2022.2080587"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"3227","DOI":"10.1113\/JP282780","article-title":"The 70-year Search for the Voltage-sensing Mechanism of Ion Channels","volume":"600","author":"Catacuzzeno","year":"2022","journal-title":"J. Physiol."},{"key":"ref_108","doi-asserted-by":"crossref","unstructured":"Varga, Z., Juh\u00e1sz, T., Matta, C., Fodor, J., Katona, \u00c9., Bartok, A., Ol\u00e1h, T., Sebe, A., Csernoch, L., and Panyi, G. (2011). Switch of Voltage-Gated K+ Channel Expression in the Plasma Membrane of Chondrogenic Cells Affects Cytosolic Ca2+-Oscillations and Cartilage Formation. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0027957"},{"key":"ref_109","doi-asserted-by":"crossref","unstructured":"Suzuki, Y., Yamamura, H., Imaizumi, Y., Clark, R.B., and Giles, W.R. (2020). K+ and Ca2+ Channels Regulate Ca2+ Signaling in Chondrocytes: An Illustrated Review. Cells, 9.","DOI":"10.3390\/cells9071577"},{"key":"ref_110","doi-asserted-by":"crossref","unstructured":"Liang, H.-Y., Yin, H.-X., Li, S.-F., Chen, Y., Zhao, Y.-J., Hu, W., and Zhou, R.-P. (2022). Calcium-Permeable Channels Cooperation for Rheumatoid Arthritis: Therapeutic Opportunities. Biomolecules, 12.","DOI":"10.3390\/biom12101383"},{"key":"ref_111","doi-asserted-by":"crossref","unstructured":"Xu, Y., and Chen, F. (2021). Acid-Sensing Ion Channel-1a in Articular Chondrocytes and Synovial Fibroblasts: A Novel Therapeutic Target for Rheumatoid Arthritis. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.580936"},{"key":"ref_112","doi-asserted-by":"crossref","unstructured":"Galindo, T., Reyna, J., and Weyer, A. (2018). Evidence for Transient Receptor Potential (TRP) Channel Contribution to Arthritis Pain and Pathogenesis. Pharmaceuticals, 11.","DOI":"10.3390\/ph11040105"},{"key":"ref_113","doi-asserted-by":"crossref","unstructured":"Li, Z., Huang, Z., and Bai, L. (2021). The P2X7 Receptor in Osteoarthritis. Front. Cell Dev. Biol., 9.","DOI":"10.3389\/fcell.2021.628330"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1016\/bs.ctm.2016.10.003","article-title":"Role of Piezo Channels in Joint Health and Injury","volume":"Volume 79","author":"Lee","year":"2017","journal-title":"Current Topics in Membranes"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"1096","DOI":"10.1038\/s41467-018-03502-7","article-title":"Voltage Gating of Mechanosensitive PIEZO Channels","volume":"9","author":"Moroni","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"E5114","DOI":"10.1073\/pnas.1414298111","article-title":"Synergy between Piezo1 and Piezo2 Channels Confers High-Strain Mechanosensitivity to Articular Cartilage","volume":"111","author":"Lee","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"21592","DOI":"10.1073\/pnas.1908981116","article-title":"L-Type Voltage-Gated Ca2+ Channel CaV1.2 Regulates Chondrogenesis during Limb Development","volume":"116","author":"Atsuta","year":"2019","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_118","doi-asserted-by":"crossref","unstructured":"Parisi, C., Chandaria, V.V., and Nowlan, N.C. (2018). Blocking Mechanosensitive Ion Channels Eliminates the Effects of Applied Mechanical Loading on Chick Joint Morphogenesis. Philos. Trans. R. Soc. B Biol. Sci., 373.","DOI":"10.1098\/rstb.2017.0317"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.bpj.2016.11.013","article-title":"GsMTx4: Mechanism of Inhibiting Mechanosensitive Ion Channels","volume":"112","author":"Gnanasambandam","year":"2017","journal-title":"Biophys. J."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1002\/jbmr.4198","article-title":"Piezo 1 Inactivation in Chondrocytes Impairs Trabecular Bone Formation","volume":"36","author":"Hendrickx","year":"2021","journal-title":"J. Bone Miner. Res."},{"key":"ref_121","doi-asserted-by":"crossref","unstructured":"Xu, X., Liu, S., Liu, H., Ru, K., Jia, Y., Wu, Z., Liang, S., Khan, Z., Chen, Z., and Qian, A. (2021). Piezo Channels: Awesome Mechanosensitive Structures in Cellular Mechanotransduction and Their Role in Bone. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22126429"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1146\/annurev-physiol-022516-034038","article-title":"Regulation of BK Channels by Beta and Gamma Subunits","volume":"81","author":"Lingle","year":"2019","journal-title":"Annu. Rev. Physiol."},{"key":"ref_123","doi-asserted-by":"crossref","unstructured":"Orfali, R., and Albanyan, N. (2023). Ca2+-Sensitive Potassium Channels. Molecules, 28.","DOI":"10.3390\/molecules28020885"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"7421","DOI":"10.1002\/jcp.30413","article-title":"Transcriptome-based Screening of Ion Channels and Transporters in a Migratory Chondroprogenitor Cell Line Isolated from Late-stage Osteoarthritic Cartilage","volume":"236","author":"Matta","year":"2021","journal-title":"J. Cell Physiol."},{"key":"ref_125","doi-asserted-by":"crossref","unstructured":"Haidar, O., O\u2019Neill, N., Staunton, C.A., Bavan, S., O\u2019Brien, F., Zouggari, S., Sharif, U., Mobasheri, A., Kumagai, K., and Barrett-Jolley, R. (2020). Pro-Inflammatory Cytokines Drive Deregulation of Potassium Channel Expression in Primary Synovial Fibroblasts. Front. Physiol., 11.","DOI":"10.3389\/fphys.2020.00226"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1186\/s12964-019-0487-3","article-title":"N-Methyl-D-Aspartate (NMDA) Receptor Expression and Function Is Required for Early Chondrogenesis","volume":"17","author":"Matta","year":"2019","journal-title":"Cell Commun. Signal."},{"key":"ref_127","doi-asserted-by":"crossref","unstructured":"Lewis, R., and Barrett-Jolley, R. (2015). Changes in Membrane Receptors and Ion Channels as Potential Biomarkers for Osteoarthritis. Front. Physiol., 6.","DOI":"10.3389\/fphys.2015.00357"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"110143","DOI":"10.1016\/j.cellsig.2021.110143","article-title":"IL-1\u03b2 Induces Changes in Expression of Core Circadian Clock Components PER2 and BMAL1 in Primary Human Chondrocytes through the NMDA Receptor\/CREB and NF-\u039aB Signalling Pathways","volume":"87","author":"Alhilali","year":"2021","journal-title":"Cell Signal"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1146\/annurev-biochem-060614-033910","article-title":"The Molecular Basis of G Protein\u2013Coupled Receptor Activation","volume":"87","author":"Weis","year":"2018","journal-title":"Annu. Rev. Biochem."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1038\/s41392-020-00435-w","article-title":"G Protein-Coupled Receptors: Structure- and Function-Based Drug Discovery","volume":"6","author":"Yang","year":"2021","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"R39","DOI":"10.1530\/JME-14-0093","article-title":"Role of G-Proteins in the Differentiation of Epiphyseal Chondrocytes","volume":"53","author":"Chagin","year":"2014","journal-title":"J. Mol. Endocrinol."},{"key":"ref_132","doi-asserted-by":"crossref","unstructured":"He, Q., Shumate, L.T., Matthias, J., Aydin, C., Wein, M.N., Spatz, J.M., Goetz, R., Mohammadi, M., Plagge, A., and Divieti Pajevic, P. (2019). A G Protein\u2013Coupled, IP3\/Protein Kinase C Pathway Controlling the Synthesis of Phosphaturic Hormone FGF23. JCI Insight, 4.","DOI":"10.1172\/jci.insight.125007"},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"3673","DOI":"10.1038\/ncomms4673","article-title":"G-Protein Stimulatory Subunit Alpha and Gq\/11\u03b1 G-Proteins Are Both Required to Maintain Quiescent Stem-like Chondrocytes","volume":"5","author":"Chagin","year":"2014","journal-title":"Nat. Commun."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"e6841","DOI":"10.1002\/ccr3.6841","article-title":"Albright Hereditary Osteodystrophy: Delay in the Diagnosis of a Rare Disorder Due to Restricted Medical Services","volume":"11","author":"Noor","year":"2023","journal-title":"Clin. Case Rep."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1016\/j.bbamcr.2014.12.003","article-title":"Prostaglandin F2 Receptor (FP) Signaling Regulates Bmp Signaling and Promotes Chondrocyte Differentiation","volume":"1853","author":"Kim","year":"2015","journal-title":"Biochim. Et Biophys. Acta (BBA) Mol. Cell Res."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1016\/j.joca.2006.01.007","article-title":"The Orphan G-Protein Coupled Receptor RDC1: Evidence for a Role in Chondrocyte Hypertrophy and Articular Cartilage Matrix Turnover","volume":"14","author":"Jones","year":"2006","journal-title":"Osteoarthr. Cartil."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"8967","DOI":"10.12998\/wjcc.v9.i30.8967","article-title":"Regulation of Bone Metabolism Mediated by \u03b2-Adrenergic Receptor and Its Clinical Application","volume":"9","author":"Zhong","year":"2021","journal-title":"World J. Clin. Cases"},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"1054","DOI":"10.1002\/jcb.23436","article-title":"Increased Expression of the Histamine H 4 Receptor Subtype in Hypertrophic Differentiation of Chondrogenic ATDC5 Cells","volume":"113","author":"Yamaura","year":"2012","journal-title":"J. Cell Biochem."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"eaau8491","DOI":"10.1126\/scitranslmed.aau8491","article-title":"Paroxetine-Mediated GRK2 Inhibition Is a Disease-Modifying Treatment for Osteoarthritis","volume":"13","author":"Carlson","year":"2021","journal-title":"Sci. Transl. Med."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1124\/mol.117.111062","article-title":"G Protein-Coupled Receptors as Targets for Approved Drugs: How Many Targets and How Many Drugs?","volume":"93","author":"Sriram","year":"2018","journal-title":"Mol. Pharmacol."},{"key":"ref_141","doi-asserted-by":"crossref","unstructured":"Nordberg, R.C., Mellor, L.F., Krause, A.R., Donahue, H.J., and Loboa, E.G. (2019). LRP Receptors in Chondrocytes Are Modulated by Simulated Microgravity and Cyclic Hydrostatic Pressure. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0223245"},{"key":"ref_142","doi-asserted-by":"crossref","unstructured":"Gao, Y., Chen, N., Fu, Z., and Zhang, Q. (2023). Progress of Wnt Signaling Pathway in Osteoporosis. Biomolecules, 13.","DOI":"10.3390\/biom13030483"},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1007\/s00223-017-0246-7","article-title":"Co-Expression of DKK-1 and Sclerostin in Subchondral Bone of the Proximal Femoral Heads from Osteoarthritic Hips","volume":"100","author":"Zarei","year":"2017","journal-title":"Calcif. Tissue Int."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"874","DOI":"10.1016\/j.joca.2011.04.014","article-title":"Increased Chondrocyte Sclerostin May Protect against Cartilage Degradation in Osteoarthritis","volume":"19","author":"Chan","year":"2011","journal-title":"Osteoarthr. Cartil."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1002\/jbmr.2059","article-title":"Reversing LRP5-Dependent Osteoporosis and SOST Deficiency\u2013Induced Sclerosing Bone Disorders by Altering WNT Signaling Activity","volume":"29","author":"Chang","year":"2014","journal-title":"J. Bone Miner. Res."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"1532","DOI":"10.1056\/NEJMoa1607948","article-title":"Romosozumab Treatment in Postmenopausal Women with Osteoporosis","volume":"375","author":"Cosman","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2015\/782382","article-title":"The Role of IL-1\u03b2 in the Bone Loss during Rheumatic Diseases","volume":"2015","author":"Ruscitti","year":"2015","journal-title":"Mediat. Inflamm."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"R37","DOI":"10.1186\/ar4466","article-title":"Low-Density Lipoprotein Receptor\u2013Related Protein 5 Governs Wnt-Mediated Osteoarthritic Cartilage Destruction","volume":"16","author":"Shin","year":"2014","journal-title":"Arthritis Res. Ther."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1007\/s00223-020-00739-7","article-title":"Targeting Dysregulation of Metalloproteinase Activity in Osteoarthritis","volume":"109","author":"Yamamoto","year":"2021","journal-title":"Calcif. Tissue Int."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1096\/fj.12-216671","article-title":"LRP-1-mediated Endocytosis Regulates Extracellular Activity of ADAMTS-5 in Articular Cartilage","volume":"27","author":"Yamamoto","year":"2013","journal-title":"FASEB J."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"1246","DOI":"10.1002\/art.40080","article-title":"Inhibition of Shedding of Low-Density Lipoprotein Receptor\u2013Related Protein 1 Reverses Cartilage Matrix Degradation in Osteoarthritis","volume":"69","author":"Yamamoto","year":"2017","journal-title":"Arthritis Rheumatol."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"667","DOI":"10.21873\/invivo.13127","article-title":"Ca2+\/Calmodulin-Dependent Protein Kinase II Inhibitor KN-93 Enhances Chondrogenesis of Bone Marrow Mesenchymal Stem Cells and Delays Chondrogenic Hypertrophy","volume":"37","author":"Wuttisiriboon","year":"2023","journal-title":"Vivo"},{"key":"ref_153","doi-asserted-by":"crossref","unstructured":"Karabicici, M., Azbazdar, Y., Iscan, E., and Ozhan, G. (2021). Misregulation of Wnt Signaling Pathways at the Plasma Membrane in Brain and Metabolic Diseases. Membranes, 11.","DOI":"10.3390\/membranes11110844"},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1007\/s12016-020-08829-y","article-title":"The Roles of Orphan G Protein-Coupled Receptors in Autoimmune Diseases","volume":"60","author":"Zhao","year":"2021","journal-title":"Clin. Rev. Allergy Immunol."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/j.bone.2012.09.029","article-title":"Wnt\/\u03b2-Catenin Signaling Activates Bone Morphogenetic Protein 2 Expression in Osteoblasts","volume":"52","author":"Zhang","year":"2013","journal-title":"Bone"},{"key":"ref_156","first-page":"40","article-title":"Role of Signaling Pathways in Age-Related Orthopedic Diseases: Focus on the Fibroblast Growth Factor Family","volume":"11","author":"Li","year":"2024","journal-title":"Mil. Med. Res."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"1052","DOI":"10.1111\/bcp.13867","article-title":"Pharmacology of Bisphosphonates","volume":"85","author":"Cremers","year":"2019","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"192","DOI":"10.2174\/1573403X14666180619103258","article-title":"Role of Bisphosphonates in Vascular Calcification and Bone Metabolism: A Clinical Summary","volume":"14","author":"Dayanand","year":"2018","journal-title":"Curr. Cardiol. Rev."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1038\/s41392-023-01467-8","article-title":"Targeting Strategies for Bone Diseases: Signaling Pathways and Clinical Studies","volume":"8","author":"Xu","year":"2023","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"848","DOI":"10.1016\/j.bone.2007.12.225","article-title":"Visualizing Mineral Binding and Uptake of Bisphosphonate by Osteoclasts and Non-Resorbing Cells","volume":"42","author":"Coxon","year":"2008","journal-title":"Bone"},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"1032","DOI":"10.4065\/83.9.1032","article-title":"Bisphosphonates: Mechanism of Action and Role in Clinical Practice","volume":"83","author":"Drake","year":"2008","journal-title":"Mayo Clin. Proc."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1007\/s00223-012-9570-0","article-title":"Bisphosphonate Binding Affinity Affects Drug Distribution in Both Intracortical and Trabecular Bone of Rabbits","volume":"90","author":"Turek","year":"2012","journal-title":"Calcif. Tissue Int."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"115711","DOI":"10.1016\/j.bone.2020.115711","article-title":"Bisphosphonates in Veterinary Medicine: The New Horizon for Use","volume":"142","author":"Suva","year":"2021","journal-title":"Bone"},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1007\/s00198-021-06160-6","article-title":"Evaluation of Estimated Glomerular Function (EGFR) versus Creatinine Clearance (CrCl) to Predict Acute Kidney Injury When Using Zoledronate for the Treatment of Osteoporosis","volume":"33","author":"Schini","year":"2022","journal-title":"Osteoporos. Int."},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1007\/s40273-020-00965-9","article-title":"An Updated Systematic Review of Cost-Effectiveness Analyses of Drugs for Osteoporosis","volume":"39","author":"Li","year":"2021","journal-title":"Pharmacoeconomics"},{"key":"ref_166","doi-asserted-by":"crossref","unstructured":"Shao, H., and Varamini, P. (2022). Breast Cancer Bone Metastasis: A Narrative Review of Emerging Targeted Drug Delivery Systems. Cells, 11.","DOI":"10.3390\/cells11030388"},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"4907","DOI":"10.1021\/acsabm.1c00199","article-title":"Alendronate-Decorated Nanoparticles as Bone-Targeted Alendronate Carriers for Potential Osteoporosis Treatment","volume":"4","author":"Jing","year":"2021","journal-title":"ACS Appl. Bio Mater."},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"7967","DOI":"10.2147\/IJN.S263756","article-title":"Bone-Targeted Extracellular Vesicles from Mesenchymal Stem Cells for Osteoporosis Therapy","volume":"Volume 15","author":"Wang","year":"2020","journal-title":"Int. J. Nanomed."},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"560","DOI":"10.1248\/cpb.c20-00017","article-title":"Bone-Targeted Drug Delivery Systems and Strategies for Treatment of Bone Metastasis","volume":"68","author":"Katsumi","year":"2020","journal-title":"Chem. Pharm. Bull."},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"116377","DOI":"10.1016\/j.bone.2022.116377","article-title":"Tetracyclines and Bone: Unclear Actions with Potentially Lasting Effects","volume":"159","author":"Warner","year":"2022","journal-title":"Bone"},{"key":"ref_171","doi-asserted-by":"crossref","unstructured":"Liang, Q., Zhang, P., Zhang, L., Luan, H., Li, X., Xiang, H., Jing, S., and Song, X. (2023). Development of Tetracycline-Modified Nanoparticles for Bone-Targeted Delivery of Anti-Tubercular Drug. Front. Bioeng. Biotechnol., 11.","DOI":"10.3389\/fbioe.2023.1207520"},{"key":"ref_172","doi-asserted-by":"crossref","unstructured":"Que, Y., Yang, Y., Zafar, H., and Wang, D. (2022). Tetracycline-Grafted MPEG-PLGA Micelles for Bone-Targeting and Osteoporotic Improvement. Front. Pharmacol., 13.","DOI":"10.3389\/fphar.2022.993095"},{"key":"ref_173","doi-asserted-by":"crossref","unstructured":"Hirohashi, Y., Kamijo, S., Khan, M., Ikeda, M., Oki, M., Matin, K., Rashed, F., and Aoki, K. (2021). Tetracycline, an Appropriate Reagent for Measuring Bone-Formation Activity in the Murine Model of the Streptococcus Mutans-Induced Bone Loss. Front. Cell Infect. Microbiol., 11.","DOI":"10.3389\/fcimb.2021.714366"},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1002\/jbmr.1805","article-title":"Standardized Nomenclature, Symbols, and Units for Bone Histomorphometry: A 2012 Update of the Report of the ASBMR Histomorphometry Nomenclature Committee","volume":"28","author":"Dempster","year":"2013","journal-title":"J. Bone Miner. Res."},{"key":"ref_175","doi-asserted-by":"crossref","unstructured":"Kim, Y., Kim, J., Lee, H., Shin, W.-R., Lee, S., Lee, J., Park, J.-I., Jhun, B.H., Kim, Y.-H., and Yi, S.-J. (2019). Tetracycline Analogs Inhibit Osteoclast Differentiation by Suppressing MMP-9-Mediated Histone H3 Cleavage. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20164038"},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"141ra93","DOI":"10.1126\/scitranslmed.3003720","article-title":"A Tissue Engineering Solution for Segmental Defect Regeneration in Load-Bearing Long Bones","volume":"4","author":"Reichert","year":"2012","journal-title":"Sci. Transl. Med."},{"key":"ref_177","doi-asserted-by":"crossref","unstructured":"Martin, V., Bettencourt, A.F., Santos, C., Fernandes, M.H., and Gomes, P.S. (2023). Unveiling the Osteogenic Potential of Tetracyclines: A Comparative Study in Human Mesenchymal Stem Cells. Cells, 12.","DOI":"10.3390\/cells12182244"},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"18504","DOI":"10.1073\/pnas.2007699117","article-title":"Calcium and Hydroxyapatite Binding Site of Human Vitronectin Provides Insights to Abnormal Deposit Formation","volume":"117","author":"Shin","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"096368972211449","DOI":"10.1177\/09636897221144949","article-title":"Aptamer Technology and Its Applications in Bone Diseases","volume":"32","author":"Liu","year":"2023","journal-title":"Cell Transplant."},{"key":"ref_180","doi-asserted-by":"crossref","unstructured":"Wang, Z., Yang, X., Lee, N.Z., and Cao, X. (2022). Multivalent Aptamer Approach: Designs, Strategies, and Applications. Micromachines, 13.","DOI":"10.3390\/mi13030436"},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1016\/j.jconrel.2019.12.049","article-title":"Multivalent HER2-Binding Polymer Conjugates Facilitate Rapid Endocytosis and Enhance Intracellular Drug Delivery","volume":"319","author":"Radford","year":"2020","journal-title":"J. Control. Release"},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"101529","DOI":"10.1016\/j.nantod.2022.101529","article-title":"Aptamer-Immobilized Bone-Targeting Nanoparticles in Situ Reduce Sclerostin for Osteoporosis Treatment","volume":"45","author":"Niu","year":"2022","journal-title":"Nano Today"},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1016\/j.omtn.2023.01.007","article-title":"Aptamer-Programmable Adeno-Associated Viral Vectors as a Novel Platform for Cell-Specific Gene Transfer","volume":"31","author":"Puzzo","year":"2023","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"ref_184","doi-asserted-by":"crossref","unstructured":"Xu, X., Liang, Y., Li, X., Ouyang, K., Wang, M., Cao, T., Li, W., Liu, J., Xiong, J., and Li, B. (2021). Exosome-Mediated Delivery of Kartogenin for Chondrogenesis of Synovial Fluid-Derived Mesenchymal Stem Cells and Cartilage Regeneration. Biomaterials, 269.","DOI":"10.1016\/j.biomaterials.2020.120539"},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"5645","DOI":"10.7150\/thno.63177","article-title":"Therapeutic Aptamer Targeting Sclerostin Loop3 for Promoting Bone Formation without Increasing Cardiovascular Risk in Osteogenesis Imperfecta Mice","volume":"12","author":"Wang","year":"2022","journal-title":"Theranostics"},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1038\/nm.3791","article-title":"Aptamer-Functionalized Lipid Nanoparticles Targeting Osteoblasts as a Novel RNA Interference\u2013Based Bone Anabolic Strategy","volume":"21","author":"Liang","year":"2015","journal-title":"Nat. Med."},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1038\/nm.2617","article-title":"A Delivery System Targeting Bone Formation Surfaces to Facilitate RNAi-Based Anabolic Therapy","volume":"18","author":"Zhang","year":"2012","journal-title":"Nat. Med."},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"20884","DOI":"10.1039\/C9NR02791B","article-title":"Aptamer-Functionalized Exosomes from Bone Marrow Stromal Cells Target Bone to Promote Bone Regeneration","volume":"11","author":"Luo","year":"2019","journal-title":"Nanoscale"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/15\/8339\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:26:37Z","timestamp":1760109997000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/15\/8339"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,7,30]]},"references-count":188,"journal-issue":{"issue":"15","published-online":{"date-parts":[[2024,8]]}},"alternative-id":["ijms25158339"],"URL":"https:\/\/doi.org\/10.3390\/ijms25158339","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,7,30]]}}}