[Homeostasis and Disorder of Musculoskeletal System.Enthesis formation and repair:Current understanding and perspectives for the future regenerative therapy.]

Tendons and ligaments are dense fibrous connective tissues mainly composed of type I collagen, aligned in highly ordered arrays along the axis of the tendon and ligament. The enthesis is defined as the attachment site of a tendon, ligament, joint capsule, or fascia to bone. During morphogenesis, the cell population co-expressing Scleraxis(Scx)and the SRY-box containing gene 9(Sox9)contributes to the formation of fibrocartilaginous entheses. Scx regulates tendon and ligament maturation, while Sox9 is a key regulatory factor for cartilage formation. The considerable mechanical forces transmitted through the enthesis and avascular properties of the tissue make it more prone to injuries and degenerative changes. Thus, integration of tendons or ligaments with bone following surgical repair remains a clinical challenge. In this review, we summarize the current knowledge regarding the formation, maintenance, damage, and repair of fibrocartilaginous entheses, focusing on the rotator cuff tendon-to-bone attachment sites.