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Antibodies against NGF show analgesic effects in painful knee OA, but clinical development was stopped because of side effects in the joints. Knowledge about the biologic effects of NGF on joint tissues is limited. Therefore, we explored the effects of repeated intra\u2010articular (IA) injections of NGF into na\u00efve murine knee joints on sensitization, joint innervation, and histopathology.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Na\u00efve 10\u2010 to 15\u2010week\u2010old male wildtype C57BL\/6 mice were injected with NGF (50 or 500 ng) or vehicle IA twice a week for four weeks, and effects on knee swelling, knee hyperalgesia, joint histopathology, and bone were assessed. Single cell RNA sequencing (scRNAseq) of the synovium was performed. Na\n                      <jats:sub>V<\/jats:sub>\n                      1.8\u2010tdTomato reporter mice were used to assess joint innervation. Dorsal root ganglia (DRGs) of mice underwent bulk RNAseq after three IA injections of NGF or vehicle.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Compared with vehicle, repeated IA injections of NGF caused dose\u2010dependent increases in knee swelling, knee hyperalgesia, synovial pathology, bone mineral density in the medial subchondral bone, and medial preosteophytes, but no overt cartilage damage. NGF caused increased sprouting of nociceptors in the medial synovium that was preceded by up\u2010regulation of axonal growth pathways in the DRGs. ScRNAseq of the synovium revealed up\u2010regulated genes related to neuronal sprouting, synovial fibrosis, and ossification, with a key role for lining fibroblasts.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>In na\u00efve mouse knees, NGF induced many pathologic changes observed in OA, including nociceptor sprouting, suggesting a critical role for NGF in OA pathogenesis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/art.70168","type":"journal-article","created":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T10:35:14Z","timestamp":1775471714000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Nerve Growth Factor is Sufficient to Cause Multiple Osteoarthritis\u2010Relevant Pathologic Features in Na\u00efve Murine Knee Joints"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-9864-0119","authenticated-orcid":false,"given":"Alia M.","family":"Obeidat","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Division of Rheumatology Rush University Medical Center  Chicago Illinois"},{"name":"Chicago Center on Musculoskeletal Pain (C\u2010COMP)  Chicago Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael D.","family":"Newton","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery University of Michigan  Ann Arbor"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Rheumatology Rush University Medical Center  Chicago Illinois"},{"name":"Chicago Center on Musculoskeletal Pain (C\u2010COMP)  Chicago Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baofeng","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Rheumatology University of Pennsylvania  Philadelphia"},{"name":"Translational Musculoskeletal Research Center Corp. 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