{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T06:49:55Z","timestamp":1784875795897,"version":"3.55.0"},"reference-count":45,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2023,3,29]],"date-time":"2023-03-29T00:00:00Z","timestamp":1680048000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["asbmr.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["JBMR Plus"],"published-print":{"date-parts":[[2023,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Collagen X is a non\u2010fibril collagen produced by hypertrophic chondrocytes and was believed to associate with the calcification process of growth plate cartilage. The homozygous loss of\n                    <jats:italic>Col10a1<\/jats:italic>\n                    gene in mice, however, demonstrated no remarkable effects on growth plate formation or skeletal development. To investigate the role of collagen X in human chondrocytes, we established human induced pluripotent stem cells (hiPSCs) with heterozygous (\n                    <jats:italic>COL10A1<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>+\/\u2212<\/jats:italic>\n                    <\/jats:sup>\n                    ) or homozygous (\n                    <jats:italic>COL10A1<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>\u2212\/\u2212<\/jats:italic>\n                    <\/jats:sup>\n                    ) deletions of\n                    <jats:italic>COL10A1<\/jats:italic>\n                    gene using the dual sgRNA CRISPR\/Cas9 system. Several mutant clones were established and differentiated into hypertrophic chondrocytes by a previously reported 3D induction method. No remarkable differences were observed during the differentiation process between parental and mutant cell lines, which differentiated into cells with features of hypertrophic chondrocytes, indicating that collagen X is dispensable for the hypertrophic differentiation of human chondrocytes in vitro. To investigate the effects of collagen X deficiency in vivo, chondrocyte pellets at the proliferating or prehypertrophic stage were transplanted into immunodeficient mice. Proliferating pellet\u2010derived tissues demonstrated the zonal distribution of chondrocytes with the transition to bone tissues mimicking growth plates, and the proportion of bone tended to be larger in\n                    <jats:italic>COL10A1<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>\u2212\/\u2212<\/jats:italic>\n                    <\/jats:sup>\n                    tissues. Prehypertrophic pellet\u2010derived tissues produced trabecular bone structures with features of endochondral ossification, and there was no clear difference between parental\u2010 and mutant\u2010derived tissues. A transcriptome analysis of chondrocyte pellets at the hypertrophic phase showed a lower expression of proliferating\u2010phase genes and a higher expression of calcification\u2010phase genes in\n                    <jats:italic>COL10A1<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>\u2212\/\u2212<\/jats:italic>\n                    <\/jats:sup>\n                    pellets compared with parental cell pellets. These in vitro and in vivo data suggested that collagen X is dispensable for the hypertrophic differentiation and endochondral ossification of human iPSC\u2010derived chondrocytes, though it may facilitate the differentiation process. Thus,\n                    <jats:italic>COL10A1<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>\u2212\/\u2212<\/jats:italic>\n                    <\/jats:sup>\n                    iPSC lines are useful for investigating the physiological role of collagen X in chondrocyte differentiation. \u00a9 2023 The Authors.\n                    <jats:italic>JBMR Plus<\/jats:italic>\n                    published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.\n                  <\/jats:p>","DOI":"10.1002\/jbm4.10737","type":"journal-article","created":{"date-parts":[[2023,2,21]],"date-time":"2023-02-21T12:40:26Z","timestamp":1676983226000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Collagen X Is Dispensable for Hypertrophic Differentiation and Endochondral Ossification of Human\n                    <scp>iPSC<\/scp>\n                    \u2010Derived Chondrocytes"],"prefix":"10.1093","volume":"7","author":[{"given":"Takeshi","family":"Kamakura","sequence":"first","affiliation":[{"name":"Department of Regeneration Sciences and Engineering, Institute for Life and Medical Sciences Kyoto University  Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yonghui","family":"Jin","sequence":"additional","affiliation":[{"name":"Department of Regeneration Sciences and Engineering, Institute for Life and Medical Sciences Kyoto University  Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megumi","family":"Nishio","sequence":"additional","affiliation":[{"name":"Department of Fundamental Cell Technology, Center for iPS Cell Research and Application Kyoto University  Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanae","family":"Nagata","sequence":"additional","affiliation":[{"name":"Department of Fundamental Cell Technology, Center for iPS Cell Research and Application Kyoto University  Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masayuki","family":"Fukuda","sequence":"additional","affiliation":[{"name":"Department of Regeneration Sciences and Engineering, Institute for Life and Medical Sciences Kyoto University  Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liping","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Regeneration Sciences and Engineering, Institute for Life and Medical Sciences Kyoto University  Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shunsuke","family":"Kawai","sequence":"additional","affiliation":[{"name":"Department of Fundamental Cell Technology, Center for iPS Cell Research and Application Kyoto University  Kyoto 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