{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T16:29:14Z","timestamp":1790958554196,"version":"4.1.0"},"reference-count":34,"publisher":"Portland Press Ltd.","issue":"13","license":[{"start":{"date-parts":[[2020,5,11]],"date-time":"2020-05-11T00:00:00Z","timestamp":1589155200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/2.0\/"}],"content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2020,7,17]]},"abstract":"<jats:p>One of the fundamental questions in bone biology is where osteoblasts originate and how osteoblast differentiation is regulated. The mechanism underlying which factors regulate chondrocyte to osteoblast lineage commitment remains unknown. Our data showed that Runt-related transcription factor 1 (Runx1) is expressed at different stages of both chondrocyte and osteoblast differentiation. Runx1 chondrocyte-specific knockout (Runx1f\/fCol2\u03b11-cre) mice exhibited impaired cartilage formation, decreased bone density, and an osteoporotic phenotype. The expressions of chondrocyte differentiation regulation genes, including Sox9, Ihh, CyclinD1, PTH1R, and hypertrophic chondrocyte marker genes including Col2\u03b11, Runx2, MMP13, Col10\u03b11 in the growth plate were significantly decreased in Runx1f\/fCol2\u03b11-cre mice chondrocytes. Importantly, the expression of osteoblast differentiation regulation genes including Osx, Runx2, ATF4, and osteoblast marker genes including osteocalcin (OCN) and osteopontin (OPN) were significantly decreased in the osteoblasts of Runx1f\/fCol2\u03b11-cre mice. Notably, our data showed that osteoblast differentiation regulation genes and marker genes are also expressed in chondrocytes and the expressions of these marker genes were significantly decreased in the chondrocytes of Runx1f\/fCol2\u03b11-cre mice. Our data showed that chromatin immunoprecipitation (ChIP) and promoter mapping analysis revealed that Runx1 directly binds to the Indian hedgehog homolog (Ihh) promoter to regulate its expression, indicating that Runx1 directly regulates the transcriptional expression of chondrocyte genes. Collectively, we revealed that Runx1 signals chondrocyte to osteoblast lineage commitment and promotes endochondral bone formation through enhancing both chondrogenesis and osteogenesis genes expressions, indicating Runx1 may be a therapeutic target to enhance endochondral bone formation and prevent osteoporosis fractures.<\/jats:p>","DOI":"10.1042\/bcj20200036","type":"journal-article","created":{"date-parts":[[2020,5,11]],"date-time":"2020-05-11T12:14:03Z","timestamp":1589199243000},"page":"2421-2438","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":58,"title":["Runx1 up-regulates chondrocyte to osteoblast lineage commitment and promotes bone formation by enhancing both chondrogenesis and osteogenesis"],"prefix":"10.1042","volume":"477","author":[{"given":"Chen-Yi","family":"Tang","sequence":"first","affiliation":[{"name":"Department of Metabolism and Endocrinology, Hunan Provincial Key Laboratory of Metabolic Bone Diseases, National Clinical Research Center for Metabolic Diseases, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China"},{"name":"Department of Pathology, University of Alabama at Birmingham School of Medicine, Birmingham, AL, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Alabama at Birmingham School of Medicine, Birmingham, AL, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Alabama at Birmingham School of Medicine, Birmingham, AL, U.S.A."},{"name":"Oral Biomedical Engineering Laboratory, Shanghai Stomatological Hospital, Fudan University, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinjin","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Alabama at Birmingham School of Medicine, Birmingham, AL, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Alabama at Birmingham School of Medicine, Birmingham, AL, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abigail","family":"McVicar","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Alabama at Birmingham School of Medicine, Birmingham, AL, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"McConnell","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Alabama at Birmingham School of Medicine, Birmingham, AL, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuehua","family":"Liu","sequence":"additional","affiliation":[{"name":"Oral Biomedical Engineering Laboratory, Shanghai Stomatological Hospital, Fudan University, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hou-De","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Metabolism and Endocrinology, Hunan Provincial Key Laboratory of Metabolic Bone Diseases, National Clinical Research Center for Metabolic Diseases, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2188-6958","authenticated-orcid":false,"given":"Yi-Ping","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Alabama at Birmingham School of Medicine, Birmingham, AL, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2020,7,2]]},"reference":[{"key":"2021112218091608400_BCJ-2020-0036C1","doi-asserted-by":"publisher","first-page":"1157","DOI":"10.1038\/ncb3067","article-title":"A subset of chondrogenic cells provides early mesenchymal progenitors in growing bones","volume":"16","year":"2014","journal-title":"Nat. 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