Inhibition of Integrin αvβ6 Activation of TGF‐β Attenuates Tendinopathy. Issue 11 (15th February 2022)

• Record Type: Journal Article
• Authors: Wang, Xiao; Liu, Shen; Yu, Tao; An, Senbo; Deng, Ruoxian; Tan, Xiaohua; Crane, Janet; Zhang, Weixin; Pan, Dayu; Wan, Mei; Carr, Andrew; Cao, Xu
• Is Part Of: Advanced science. Volume 9:Issue 11(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-02-15
• Subjects: integrin αvβ6 -- tendinopathy -- transforming growth factor‐beta; Science -- Periodicals; 505
• DOI: 10.1002/advs.202104469
• Languages: English
• ISSNs: 2198-3844

Abstract

Abstract: Tendinopathy is a common tendon disorder that causes pain and impairs function. It is the most common reason for consultation with musculoskeletal specialists. The available therapies for tendinopathy are limited in number and efficacy and have unclear cellular and molecular mechanisms. Here it is shown that transforming growth factor‐beta (TGF‐ β ) activated by integrin α v β 6 promotes tendinopathy in mice. Excessive active TGF‐ β is found during tendinopathy progression, which led to tenocytes' phenotype transition to chondrocytes. Transgenic expression of active TGF‐ β in tendons induced spontaneous tendinopathy, whereas systemic injection of a TGF‐ β neutralizing antibody attenuated tendinopathy. Inducible knockout of the TGF‐ β type 2 receptor gene (Tgfbr2) in tenocytes inhibited tendinopathy progression in mice. Moreover, it is found that integrin α v β 6 induces TGF‐ β activation in response to mechanical load in tendons. Conditional knockout of the integrin α v gene in tendons prevented tendinopathy in mice. The study suggests that integrin α v β 6 activation of TGF‐ β is the mechanism of tendinopathy, and that integrin α v β 6 may be a therapeutic target in tendinopathy. Abstract : In the context of physiological load, the latency‐associated protein (LAP) is linked with tenocytes via arginine‐glycine‐ascorbate amino acid (RGD)‐ α v β 6 associate, and TGF‐ β remains latent. Excessive or repetitive loading induces conformation changes of LAP, leading to the release of active TGF‐ β which binds to its receptor and initiates proliferation, apoptosis, and chondrogenesis of tenocytes as well as excessive vessel formation in tendons.