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Osteoarthritis animal models can recapitulate aspects of human disease progression and are used to test efficacy of drugs, biomaterials, and cell therapies. The rat medial meniscus transection (MMT) model is a surgically induced posttraumatic osteoarthritis model commonly used for preclinical therapeutic screening. We describe herein, the qualitative and quantitative changes to articular cartilage, subchondral bone, and formation of osteophytes at early\u2010, mid\u2010, and late\u2010stages of osteoarthritis progression. Tibia of MMT\u2010operated animals showed proteoglycan loss and fibrillation along articular cartilage surfaces as early as 3\u2010weeks post\u2010surgery. With contrast\u2010enhanced micro\u2010CT technique, quantitative, 3\u2010dimensional analysis of the tibia showed that the articular cartilage thickened at 3\u2010 and 6\u2010weeks post\u2010surgery and decreased at 12\u2010weeks post\u2010surgery. This decreased cartilage thickness corresponded with increased lesions in the articular cartilage that led to its full degradation and exposing the subchondral bone layer. Further, subchondral bone thickening was significant at 6\u2010weeks post\u2010surgery and followed cartilage damage. Osteophytes were found as early as 3\u2010weeks post\u2010surgery and coincided with articular cartilage degradation. Cartilaginous osteophytes preceded mineralization, suggesting endochondral ossification. The rat MMT model has predominantly been used out to 3\u2010weeks, and most studies determined the effect of therapies to delay or prevent the onset of osteoarthritis. We provide evidence that an extension of the rat MMT model out to 6\u2010 and 12\u2010weeks more resembled severe phenotypes of human osteoarthritis. Thus, evaluating novel therapeutics at late\u2010stage will be important for eventual clinical translation.<\/jats:p>","DOI":"10.1002\/jor.25969","type":"journal-article","created":{"date-parts":[[2024,10,10]],"date-time":"2024-10-10T12:53:09Z","timestamp":1728564789000},"page":"102-116","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Osteoarthritis early\u2010, mid\u2010 and late\u2010stage progression in the rat medial meniscus transection model"],"prefix":"10.1002","volume":"43","author":[{"given":"Jay M.","family":"McKinney","sequence":"first","affiliation":[{"name":"Atlanta Veteran's Affairs Medical Center Decatur Georgia USA"},{"name":"Department of Orthopaedics Emory University Atlanta Georgia USA"},{"name":"Wallace H. Coulter Department of Biomedical Engineering Georgia Institute of Technology and Emory University Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krishna A.","family":"Pucha","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics Emory University Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabrice C.","family":"Bernard","sequence":"additional","affiliation":[{"name":"Wallace H. Coulter Department of Biomedical Engineering Georgia Institute of Technology and Emory University Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Brandon Dixon","sequence":"additional","affiliation":[{"name":"Department of Mechanical Engineering Georgia Institute of Technology Atlanta Georgia USA"},{"name":"Parker H. Petit Institute for Bioengineering and Bioscience Georgia Institute of Technology Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9079-9087","authenticated-orcid":false,"given":"Thanh N.","family":"Doan","sequence":"additional","affiliation":[{"name":"Atlanta Veteran's Affairs Medical Center Decatur Georgia USA"},{"name":"Department of Orthopaedics Emory University Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nick J.","family":"Willett","sequence":"additional","affiliation":[{"name":"Atlanta Veteran's Affairs Medical Center Decatur Georgia USA"},{"name":"Department of Orthopaedics Emory University Atlanta Georgia USA"},{"name":"Wallace H. Coulter Department of Biomedical Engineering Georgia Institute of Technology and Emory University Atlanta Georgia USA"},{"name":"Parker H. Petit Institute for Bioengineering and Bioscience Georgia Institute of Technology Atlanta Georgia USA"},{"name":"Phil and Penny Knight Campus for Accelerating Scientific Impact University of Oregon Eugene Oregon USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,10,10]]},"reference":[{"issue":"10","key":"e_1_2_8_2_1","article-title":"A review of non\u2010surgical pain management in osteoarthritis","volume":"12","author":"Jadidi 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