Zhang Qianyu, Song Qimin, Li Zeyin, Wu Xinyi, Chen Yuxiong, Lin Hui
School of Basic Medical Sciences, Jiangxi Medical College, Nanchang University, Nanchang, China.
Queen Mary School, Nanchang University, Nanchang, China.
Front Cell Dev Biol. 2025 May 26;13:1612950. doi: 10.3389/fcell.2025.1612950. eCollection 2025.
Fibroblasts are integral to the pathological processes underlying abnormal bone formation, including heterotopic ossification (HO), ankylosing spondylitis (AS), and ossification of the posterior longitudinal ligament (OPLL). This review summarized the diverse roles of fibroblasts, from their transdifferentiation into osteoblast-like cells to their influence on inflammatory and mechanical signal transduction pathways, including those mediated by BMP, TGF-β, and Wnt/β-catenin. In particular, senescent fibroblasts can secrete Activin A to activate the BMP pathway to drive HO formation, and fibroblasts can also differentiate into osteoblasts via interactions among the TGF-β1, BMP-2, and FGF-2 pathways. In AS and OPLL, fibroblasts respond to inflammatory signals and mechanical stress, contributing to pathological bone formation through extracellular matrix remodeling and osteogenic gene expression. In rare cases, fibroblast-mediated abnormal ossification also occurs in diffuse idiopathic skeletal hyperostosis (DISH) and systemic sclerosis (SSc). Therapeutic strategies targeting fibroblast signaling pathways, inflammation, and senescence are highlighted as potential interventions to mitigate these conditions.
成纤维细胞在异常骨形成的病理过程中不可或缺，这些病理过程包括异位骨化（HO）、强直性脊柱炎（AS）和后纵韧带骨化（OPLL）。本综述总结了成纤维细胞的多种作用，从其向成骨样细胞的转分化到其对炎症和机械信号转导途径的影响，包括由骨形态发生蛋白（BMP）、转化生长因子-β（TGF-β）和Wnt/β-连环蛋白介导的信号转导途径。特别是，衰老的成纤维细胞可分泌激活素A以激活BMP途径来驱动HO形成，并且成纤维细胞还可通过TGF-β1、BMP-2和FGF-2途径之间的相互作用分化为成骨细胞。在AS和OPLL中，成纤维细胞对炎症信号和机械应力作出反应，通过细胞外基质重塑和成骨基因表达促进病理性骨形成。在罕见情况下，成纤维细胞介导的异常骨化也发生在弥漫性特发性骨肥厚（DISH）和系统性硬化症（SSc）中。针对成纤维细胞信号通路、炎症和衰老的治疗策略被强调为减轻这些病症的潜在干预措施。
