As an essential member of the neurotrophic factor family, nerve growth factor (NGF) plays multifaceted regulatory roles in the pathological processes of bone and joint diseases through its dual signaling mechanisms involving high-affinity receptor TrkA and low-affinity receptor p75NTR. 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-induced bone formation through the Wnt/β-catenin signaling pathway and regulates osteogenic differentiation through the BMP-2/Smads pathway. Second, by activating the transient receptor potential vanilloid 1 (TRPV1) channel, NGF promotes the release of pain mediators like calcitonin gene-related 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-1β (IL-1β) and tumor necrosis factor-α (TNF-α). Consequently, the pleiotropic nature of NGF renders therapeutic strategies targeting it a double-edged 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.
Wu et al. (Mon,) studied this question.