{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Type X collagen, encoded by the COL10A1 gene, is a specialized extracellular matrix protein that defines the hypertrophic chondrocyte phenotype during endochondral ossification. It is expressed exclusively by chondrocytes in the hypertrophic zone, where it contributes to cartilage matrix remodeling, mineralization, and the subsequent invasion of blood vessels, all of which are crucial for normal bone growth and skeletal development."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Its expression is tightly regulated at the transcriptional level: the master osteogenic transcription factor RUNX2 directly transactivates the COL10A1 promoter to drive hypertrophic differentiation"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}, {"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "; conversely, SOX9, which is essential for early chondrogenesis, represses premature COL10A1 expression in immature chondrocytes and must be downregulated to allow full hypertrophy."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "5", "end_ref": "7"}]}, {"type": "t", "text": " Moreover, under hypoxic conditions, HIF‑2α emerges as a potent transactivator of COL10A1 along with other factors (e.g., MMP13 and VEGF), thereby linking oxygen-sensing pathways with the regulation of matrix degradation and vascular invasion."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In addition to its canonical role in skeletal development and remodeling, aberrant COL10A1 expression is observed in pathological conditions. For instance, increased COL10A1 is found in human osteoarthritic cartilage, signifying chondrocyte hypertrophy and matrix instability during disease progression"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": ", and its up‐regulation in non‐skeletal tissues has been linked to enhanced migration, invasion, and epithelial–mesenchymal transition in gastric cancer, likely through the TGF‑β1–SOX9 signaling axis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": " Furthermore, genetic conditions that disrupt normal RUNX2 function, such as campomelic dysplasia, are associated with dysregulated COL10A1 expression and abnormal chondrocyte hypertrophy."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these findings underscore that COL10A1 is not only a hallmark marker of terminal chondrocyte differentiation but also a functional mediator of cartilage matrix modification, mineralization, and vascularization during bone formation. Dysregulation of COL10A1 expression is closely associated with both skeletal dysplasias and degenerative joint diseases, as well as with aberrant cellular behaviors in certain cancers.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Toshihisa Komori "}, {"type": "b", "children": [{"type": "t", "text": "Regulation of bone development and extracellular matrix protein genes by RUNX2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Tissue Res (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00441-009-0832-8"}], "href": "https://doi.org/10.1007/s00441-009-0832-8"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19649655"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19649655"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Taku Saito, Atsushi Fukai, Akihiko Mabuchi, et al. 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