{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,25]],"date-time":"2026-10-25T01:22:33Z","timestamp":1792891353338,"version":"4.5.0"},"reference-count":90,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2019,6,12]],"date-time":"2019-06-12T00:00:00Z","timestamp":1560297600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"},{"start":{"date-parts":[[2019,6,12]],"date-time":"2019-06-12T00:00:00Z","timestamp":1560297600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["asbmr.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2019,9,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>RUNX2 is a transcription factor critical for chondrocyte maturation and normal endochondral bone formation. It promotes the expression of factors catabolic to the cartilage extracellular matrix and is upregulated in human osteoarthritic cartilage and in murine articular cartilage following joint injury. To date, in vivo studies of RUNX2 overexpression in cartilage have been limited to forced expression in osteochondroprogenitor cells preventing investigation into the effects of chondrocyte-specific RUNX2 overexpression in postnatal articular cartilage. Here, we used the Rosa26Runx2 allele in combination with the inducible Col2a1CreERT2 transgene or the inducible AcanCreERT2 knock-in allele to achieve chondrocyte-specific RUNX2 overexpression (OE) during embryonic development or in the articular cartilage of adult mice, respectively. RUNX2 OE was induced at embryonic day 13.5 (E13.5) for all developmental studies. Histology and in situ hybridization analyses suggest an early onset of chondrocyte hypertrophy and accelerated terminal maturation in the limbs of the RUNX2 OE embryos compared to control embryos. For all postnatal studies, RUNX2 OE was induced at 2 months of age. Surprisingly, no histopathological signs of cartilage degeneration were observed even 6 months following induction of RUNX2 OE. Using the meniscal\/ligamentous injury (MLI), a surgical model of knee joint destabilization and meniscal injury, however, we found that RUNX2 OE accelerates the progression of cartilage degeneration following joint trauma. One month following MLI, the numbers of MMP13-positive and TUNEL-positive chondrocytes were significantly greater in the articular cartilage of the RUNX2 OE joints compared to control joints and 2 months following MLI, histomorphometry and Osteoarthritis Research Society International (OARSI) scoring revealed decreased cartilage area in the RUNX2 OE joints. Collectively, these results suggest that although RUNX2 overexpression alone may not be sufficient to initiate the OA degenerative process, it may predetermine the rate of OA onset and\/or progression following traumatic joint injury. \u00a9 2019 American Society for Bone and Mineral Research.<\/jats:p>","DOI":"10.1002\/jbmr.3737","type":"journal-article","created":{"date-parts":[[2019,6,12]],"date-time":"2019-06-12T14:16:16Z","timestamp":1560348976000},"page":"1676-1689","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":71,"title":["Chondrocyte-Specific RUNX2 Overexpression Accelerates Post-traumatic Osteoarthritis Progression in Adult Mice"],"prefix":"10.1093","volume":"34","author":[{"given":"Sarah E","family":"Catheline","sequence":"first","affiliation":[{"name":"Department of Pathology and Laboratory Medicine University of Rochester Medical Center Rochester NY USA"},{"name":"Center for Musculoskeletal Research University of Rochester Medical Center Rochester NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donna","family":"Hoak","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics and Rehabilitation University of Rochester Medical Center Rochester NY USA"},{"name":"Center for Musculoskeletal Research University of Rochester Medical Center Rochester NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics and Rehabilitation University of Rochester Medical Center Rochester NY USA"},{"name":"Center for Musculoskeletal Research University of Rochester Medical Center Rochester NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John P","family":"Ketz","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics and Rehabilitation University of Rochester Medical Center Rochester NY USA"},{"name":"Center for Musculoskeletal Research University of Rochester Medical Center Rochester NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew J","family":"Hilton","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery Duke University Durham NC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J","family":"Zuscik","sequence":"additional","affiliation":[{"name":"Orthopedic Research Center University of Colorado Anschutz Medical Campus Aurora CO USA"},{"name":"Department of Orthopedics University of Colorado Anschutz Medical Campus Aurora CO USA"},{"name":"Department of Orthopaedics and Rehabilitation University of Rochester Medical Center Rochester NY USA"},{"name":"Center for Musculoskeletal Research University of Rochester Medical Center Rochester NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer H","family":"Jonason","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics and Rehabilitation University of Rochester Medical Center Rochester NY USA"},{"name":"Center for Musculoskeletal Research University of Rochester Medical Center Rochester NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2019,6,12]]},"reference":[{"issue":"21","key":"2024021014440415700_jbmr3737-bib-0001","doi-asserted-by":"crossref","first-page":"2813","DOI":"10.1101\/gad.1017802","article-title":"The transcription factor Sox9 has essential roles in successive steps of the chondrocyte differentiation pathway and is required for expression of Sox5 and Sox6","volume":"16","author":"Akiyama","year":"2002","journal-title":"Genes Dev"},{"issue":"16","key":"2024021014440415700_jbmr3737-bib-0002","doi-asserted-by":"crossref","first-page":"4999","DOI":"10.1128\/MCB.00695-08","article-title":"L-Sox5 and Sox6 drive expression of the aggrecan gene in cartilage by securing binding of Sox9 to a far-upstream 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