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This review systematically examines the profound impact of NGF on bone and joint diseases in multiple aspects, such as bone remodeling, pain perception, and angiogenesis. First, NGF promotes mechanical stress\u2010induced bone formation through the Wnt\/\u03b2\u2010catenin signaling pathway and regulates osteogenic differentiation through the BMP\u20102\/Smads pathway. Second, by activating the transient receptor potential vanilloid 1 (TRPV1) channel, NGF promotes the release of pain mediators like calcitonin gene\u2010related peptide (CGRP) and substance P (SP). This leads to both peripheral and central sensitization, thereby establishing NGF as a key mediator of chronic pain in osteoarthritis (OA) and intervertebral disc degeneration (IVDD). Third, NGF engages in complex interactions with key inflammatory factors such as interleukin\u20101\u03b2 (IL\u20101\u03b2) and tumor necrosis factor\u2010\u03b1 (TNF\u2010\u03b1). Consequently, the pleiotropic nature of NGF renders therapeutic strategies targeting it a double\u2010edged sword. This review summarizes the complex regulatory role of NGF in bone and joint diseases and proposes some potential research directions based on the current research status.<\/jats:p>","DOI":"10.1002\/cbf.70237","type":"journal-article","created":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T07:46:15Z","timestamp":1780904775000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Nerve Growth Factor: A Multifaceted Regulator of Pain, Inflammation, and Tissue Remodeling in Bone and Joint Disorders"],"prefix":"10.1002","volume":"44","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3661-8593","authenticated-orcid":false,"given":"Zuping","family":"Wu","sequence":"first","affiliation":[{"name":"School of Stomatology Stomatology Hospital, Zhejiang University School of Medicine, Clinical Research Center for Oral Diseases of Zhejiang Province, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center 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