2f:I[703058,["/_next/static/immutable/chunks/3bhq_5eh1d760.js","/_next/static/immutable/chunks/1855-ogyi8eh4.js","/_next/static/immutable/chunks/2pfsjpn6k6zlg.js","/_next/static/immutable/chunks/26c7v3_3uwnwu.js","/_next/static/immutable/chunks/25a3ozcrvi1ff.js","/_next/static/immutable/chunks/2r4wx50nvjh_4.js","/_next/static/immutable/chunks/23fsw06hsi5b1.js","/_next/static/immutable/chunks/06_yt270h41rg.js","/_next/static/immutable/chunks/3ezsiz-7shkna.js","/_next/static/immutable/chunks/20x2y96ldu5wx.js","/_next/static/immutable/chunks/2lxntcm3pd1_h.js","/_next/static/immutable/chunks/00dgco8irq3jw.js","/_next/static/immutable/chunks/00nwe-kq0rboc.js","/_next/static/immutable/chunks/2051ffx3xzio9.js"],"PaperListPageClient"] 30:T5df,Nerve growth factor (NGF), a key mediator of pain, is increased in osteoarthritic (OA) joints. 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-articular (IA) injections of NGF into naïve murine knee joints on sensitization, joint innervation, and histopathology. Naïve 10- to 15-week-old 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 Compared with vehicle, repeated IA injections of NGF caused dose-dependent 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-regulation of axonal growth pathways in the DRGs. ScRNAseq of the synovium revealed up-regulated genes related to neuronal sprouting, synovial fibrosis, and ossification, with a key role for lining fibroblasts. In naïve mouse knees, NGF induced many pathologic changes observed in OA, including nociceptor sprouting, suggesting a critical role for NGF in OA pathogenesis.31:T94d, Objective Nerve growth factor (NGF), a key mediator of pain, is increased in osteoarthritic (OA) joints. 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‐articular (IA) injections of NGF into naïve murine knee joints on sensitization, joint innervation, and histopathology. Methods Naïve 10‐ to 15‐week‐old 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 V 1.8‐tdTomato 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. Results Compared with vehicle, repeated IA injections of NGF caused dose‐dependent 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‐regulation of axonal growth pathways in the DRGs. ScRNAseq of the synovium revealed up‐regulated genes related to neuronal sprouting, synovial fibrosis, and ossification, with a key role for lining fibroblasts. Conclusion In naïve mouse knees, NGF induced many pathologic changes observed in OA, including nociceptor sprouting, suggesting a critical role for NGF in OA pathogenesis. 25:[[["$","script","0",{"type":"application/ld+json","dangerouslySetInnerHTML":{"__html":"{\"@context\":\"https://schema.org\",\"@type\":\"CollectionPage\",\"name\":\"Nerve Growth Factor: modality Research & Clinical Takeaways\",\"description\":\"Explore peer-reviewed papers on Nerve Growth Factor (modality). Clinician-written summaries and actionable practice insights. 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NGF caused increased sprouting of nociceptors in the medial synovium that was preceded by up-regulation of axonal growth pathways in the DRGs. ScRNAseq of the synovium revealed up-regulated genes related to neuronal sprouting, synovial fibrosis, and ossification, with a key role for lining fibroblasts.","abstract":"$30","keywords":[],"pubmed_id":"41940477","conclusions":"In naïve mouse knees, NGF induced many pathologic changes observed in OA, including nociceptor sprouting, suggesting a critical role for NGF in OA pathogenesis.","publication_date":"2026-04-06T00:00:00"},"crossref":{"DOI":"10.1002/art.70168","URL":"https://doi.org/10.1002/art.70168","ISSN":["2326-5191","2326-5205"],"link":[{"URL":"https://acrjournals.onlinelibrary.wiley.com/doi/pdf/10.1002/art.70168","content-type":"application/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https://acrjournals.onlinelibrary.wiley.com/doi/full-xml/10.1002/art.70168","content-type":"application/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https://acrjournals.onlinelibrary.wiley.com/doi/pdf/10.1002/art.70168","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"page":null,"type":"journal-article","issue":null,"score":1,"title":["Nerve Growth Factor is Sufficient to Cause Multiple Osteoarthritis‐Relevant Pathologic Features in Naïve Murine Knee Joints"],"author":[{"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‐COMP) Chicago Illinois"}]},{"given":"Michael D.","family":"Newton","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery University of Michigan Ann Arbor"}]},{"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‐COMP) Chicago Illinois"}]},{"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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Growth Factor","value_numeric":null},{"paper_doi":"10.1002/art.70168","tag_type":"sample_size","value":"n=not explicitly stated (multiple cohorts of male C57BL/6 mice)","value_numeric":null},{"paper_doi":"10.1002/art.70168","tag_type":"sex","value":"male","value_numeric":null},{"paper_doi":"10.1002/art.70168","tag_type":"study_design","value":"Controlled Animal Study","value_numeric":null},{"paper_doi":"10.1002/art.70168","tag_type":"warning","value":"Sample size (total N) was not explicitly reported in the abstract; the sample_size tag was omitted accordingly.","value_numeric":null},{"paper_doi":"10.1002/art.70168","tag_type":"warning","value":"Study used only male mice; findings may not apply to female biology or human OA populations without further validation.","value_numeric":null},{"paper_doi":"10.1002/art.70168","tag_type":"warning","value":"The 'practice_changing' impact flag is used cautiously — this is a preclinical animal study, but the mechanistic findings directly inform the clinical controversy around anti-NGF joint side effects.","value_numeric":null}],"summaries":{"what_studied":"Repeated intra-articular (IA) injections of NGF (50 or 500 ng, twice weekly for 4 weeks) into naïve murine knee joints were evaluated for effects on pain sensitization, joint innervation, synovial histopathology, bone, and cartilage using histology, scRNAseq, reporter mice, and bulk DRG RNAseq.","key_result":"NGF caused dose-dependent knee swelling, hyperalgesia, synovial pathology, increased medial subchondral bone mineral density, and medial preosteophytes — but no overt cartilage damage. Nociceptor sprouting in the medial synovium was preceded by upregulation of axonal growth pathways in dorsal root ganglia; scRNAseq implicated lining fibroblasts as key drivers of neuronal sprouting, synovial fibrosis, and ossification.","limitations":"- Animal model only (naïve male C57BL/6 mice); direct translation to human OA pathogenesis is uncertain.\n- Only male mice studied, limiting generalizability to female sex.\n- No cartilage damage was observed, which differs from the full OA phenotype seen in humans.","practice_takeaway":"NGF drives multiple OA-relevant joint changes — including nociceptor sprouting, synovial fibrosis, and subchondral bone remodeling — independent of cartilage damage, supporting its role early in OA pathogenesis. Clinicians should note that while anti-NGF therapies reduce pain, their joint side effects may reflect on-target biological activity of NGF in joint tissues."}}],"initialOffset":1,"fetchConfig":{"kind":"tags","tags":[{"tag_type":"modality","value":"Nerve Growth Factor"}]},"breadcrumbItems":[{"name":"Home","href":"/"},{"name":"Research Hub","href":"/hub"},{"name":"Modalities","href":"/hub/tag/modality"},{"name":"Nerve Growth Factor"}],"hrefConfig":{"basePath":"/hub/papers","webViewQueryParams":{"hub_ctx":"tag","hub_tag_type":"modality","hub_tag_value":"Nerve Growth Factor"}}}]]

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