Fibroblasts in heterotopic ossification: mechanisms and therapeutic targets

Heterotopic ossification (HO) refers to the abnormal formation of bone in non-skeletal tissues. Fibroblasts have traditionally been viewed as stationary cells primarily responsible for producing extracellular matrix during tissue repair and fibrosis. However, recent discoveries regarding their plasticity-encompassing roles in inflammation, extracellular matrix remodeling, and osteogenesis-highlight their potential as key contributors to the development of HO. In this review, we systematically summarize the diverse phenotypic and functional plasticity of fibroblasts in HO. Furthermore, we evaluate the possible interaction between fibroblasts and macrophages in pathophysiological processes and signaling pathways. Finally, we highlight the potential strategies for preventing and treating HO by targeting fibroblast activities.