The mechanisms and functions of TGF-β1 in tendon healing

Tendon injury accounts for 30% of musculoskeletal diseases and often leads to disability, pain, healthcare cost, and lost productivity. Following injury to tendon, tendon healing proceeds via three overlapping healing processes. However, due to the structural defects of the tendon itself, the tendon healing process is characterized by the formation of excessive fibrotic scar tissue, and injured tendons rarely return to native tendons, which can easily contribute to tendon reinjury. Moreover, the resulting fibrous scar is considered to be a precipitating factor for subsequent degenerative tendinopathy. Despite this, therapies are almost limited because underlying molecular mechanisms during tendon healing are still unknown. Transforming Growth Factor-β1 (TGF-β1) is known as one of most potent profibrogenic factors during tendon healing process. However, blockage TGF-β1 fails to effectively enhance tendon healing. A detailed understanding of real abilities of TGF-β1 involved in tendon healing can bring promising perspectives for therapeutic value that improve the tendon healing process. Thus, in this review, we describe recent efforts to identify and characterize the roles and mechanisms of TGF-β1 involved at each stage of the tendon healing and highlight potential roles of TGF-β1 leading to the fibrotic response to tendon injury.