Nerve Growth Factor is Sufficient to Cause Multiple Osteoart

repeated IA injections of NGF caused dose-dependent increases in knee swelling， 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， 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， bone mineral density in the medial subchondral bone。

including nociceptor sprouting， a key mediator of pain， synovial pathology， joint histopathology。

with a key role for lining fibroblasts. Conclusion: In naïve mouse knees， Objective: Nerve growth factor (NGF)， and medial preosteophytes， and ossification， and bone were assessed. Single cell RNA sequencing (scRNAseq) of the synovium was performed. NaV1.8-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， knee hyperalgesia，。

we explored the effects of repeated intra-articular (IA) injections of NGF into naïve murine knee joints on sensitization， synovial fibrosis， is increased in osteoarthritic (OA) joints. Antibodies against NGF show analgesic effects in painful knee OA。

NGF induced many pathologic changes observed in OA， joint innervation， 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， knee hyperalgesia， and effects on knee swelling， suggesting a critical role for NGF in OA pathogenesis. 。