TGF-β signaling in heterotopic ossification: the pathogenesis and the target for its treatment

Heterotopic Ossification (HO) is a complex and multifactorial pathological process characterized by abnormal bone production in areas outside the skeletal system (e.g., inside muscles, periarticular joints, ligaments, and tendons). This pathology is mainly classified as traumatic and hereditary, and it involves several signaling pathways, such as Wnt/β-catenin, BMP, hedgehog signaling, and transforming growth factor (TGF)-β family. TGF-β plays a key role in the development of HO as an important regulator of cartilage formation and differentiation, and endochondral ossification is a common manifestation of HO. Studies have shown that TGF-β can play an initiating and facilitating role in various stages of HO development, and that ectopic bone formation can be effectively reduced by systemic injection of TGF-β-neutralizing antibodies. This review summarizes the role of TGF-β signaling in the pathogenesis of HO and discusses potential preventive and therapeutic means to target TGF-β signaling.