{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T14:46:53Z","timestamp":1787755613739,"version":"build-2784847793"},"reference-count":48,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"10","content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2022,5,18]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Facet joint (FJ) osteoarthritis (FJOA) is a widely prevalent spinal disorder but its pathogenesis remains unclear, largely due to the difficulties in conducting longitudinal human studies and lack of spontaneous-FJOA animal models for mechanistic investigations. This study aimed to investigate whether spontaneous FJOA occurs in mice bearing mutant NFAT1 (nuclear factor of activated T cells 1) transcription factor.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>The lumbar FJs of 50 NFAT1-mutant mice and of 50 wild-type control mice, of both sexes, were examined by histopathology, quantitative gene expression analysis, semiquantitative immunohistochemistry, and a novel FJOA scoring system for semiquantitative assessment of the histopathologic changes at 2, 6, 12, and 18 months of age. Age-dependent and tissue-specific histopathologic and gene or protein expression changes were analyzed statistically.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>FJs in NFAT1-mutant mice displayed significantly increased expression of specific catabolic genes (p &lt; 0.05) and proteins (p &lt; 0.001) in cartilage and synovium as early as 2 months of age, followed by early osteoarthritic structural changes such as articular surface fissuring and chondro-osteophyte formation at 6 months. More severe cartilage lesions, osteophytes, subchondral bone changes, synovitis, and tissue-specific molecular alterations in FJs of NFAT1-mutant mice were observed at 12 and 18 months. Osteoarthritic structural changes were not detected in FJs of wild-type mice at any ages, although age-related cartilage degeneration was observed at 18 months. The novel FJOA scoring system had high intraobserver and interobserver reproducibility (correlation coefficients: r &gt; 0.97). Whole-joint FJOA scoring showed significantly higher OA scores in FJs of NFAT1-mutant mice compared with wild-type mice at all time points (p = 0.0033 at 2 months, p = 0.0001 at 6 months, p &lt; 0.0001 at 12 and 18 months).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>This study has identified the NFAT1-mutant mouse as a novel animal model of spontaneous FJOA with age-dependent and slowly progressing osteoarthritic features, developed the first FJOA scoring system, and elucidated the molecular mechanisms of NFAT1 mutation-induced FJOA.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical Relevance:<\/jats:title>\n                    <jats:p>This murine FJOA model resembles the features of human FJOA and may provide new insights into the pathogenesis of and therapeutic strategies for FJOA in humans.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.2106\/jbjs.21.00960","type":"journal-article","created":{"date-parts":[[2022,2,15]],"date-time":"2022-02-15T15:07:45Z","timestamp":1644937665000},"page":"928-940","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":7,"title":["Spontaneous Facet Joint Osteoarthritis in NFAT1-Mutant Mice"],"prefix":"10.2106","volume":"104","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8626-5637","authenticated-orcid":false,"given":"Jinxi","family":"Wang","sequence":"first","affiliation":[{"name":"Harrington Laboratory for Molecular Orthopedics, Department of Orthopedic Surgery, University of Kansas Medical Center, Kansas City, Kansas"},{"name":"Department of Biochemistry and Molecular Biology, University of Kansas Medical Center, Kansas City, Kansas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6159-9171","authenticated-orcid":false,"given":"Qinghua","family":"Lu","sequence":"additional","affiliation":[{"name":"Harrington Laboratory for Molecular Orthopedics, Department of Orthopedic Surgery, University of Kansas Medical Center, Kansas City, Kansas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2117-2584","authenticated-orcid":false,"given":"Matthew J.","family":"Mackay","sequence":"additional","affiliation":[{"name":"Harrington Laboratory for Molecular Orthopedics, Department of Orthopedic Surgery, University of Kansas Medical Center, Kansas City, Kansas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8454-1626","authenticated-orcid":false,"given":"Xiangliang","family":"Liu","sequence":"additional","affiliation":[{"name":"Harrington Laboratory for Molecular Orthopedics, Department of Orthopedic Surgery, University of Kansas Medical Center, Kansas City, Kansas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6249-0688","authenticated-orcid":false,"given":"Yi","family":"Feng","sequence":"additional","affiliation":[{"name":"Harrington Laboratory for Molecular Orthopedics, Department of Orthopedic Surgery, University of Kansas Medical Center, Kansas City, Kansas"},{"name":"Adams School of Dentistry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4468-4582","authenticated-orcid":false,"given":"Douglas C.","family":"Burton","sequence":"additional","affiliation":[{"name":"Marc A. 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