TGF-Β Isoforms: TGF-β1, TGF-β2 and TGF-β3 in Ligament and Tendon Healing

Abstract

Introduction. Tendon and ligament injuries affect people of all ages, including professional athletes. Tumor Growth Factor β (TGF- β) isoforms play a significant role in the regeneration of tendons and ligaments, such as through the recruitment of macrophages and fibroblasts or the regulation of the formation of extracellular matrix (ECM). Although the TGF- β family regulates signalling pathways related to the healing process, excessive TGF- β activation can lead to fibrosis and the formation of scars and adhesions. This article recapped the significance of TGF- β isoforms TGF- β1, TGF- β2, and TGF- β3 in the physiological healing of injured tendons and ligaments. Material and Methods. A total of 1434 articles were identified using the PubMed search string (TGF-β isoforms or TGF-β1 or tgfb1 or TGF-β2 or tgfb2 or TGF-β3 or tgfb3) and (tendon or ligament). Human studies, animal models and in vitro cultures were included in the search. Forty-nine published articles were included. Results. Histologic evidence demonstrated greater ligament and tendon regeneration and collagen type I expression when using TGF-β1, often leading to fibrosis. TGF-β3 inhibits the TGF-β1 and TGF-β2 by switching Smad2/3 signaling to Smad7 and CREB-1 transcription factor. There was a delay in TGF-β3 level peak compared to other isoforms. Conclusions. All 3 TGF-β isoforms seem to play a significant role in the subsequent stages of healing. We state a hypothesis that during the initial phase of tendon and ligament healing, TGF-β1 levels need to be elevated. Further, TGF-β3 may inhibit the action of TGF-β1 and TGF-β2, which leads to the inhibition of inflammation and changes in ECM production, and consequently to a reduction in the level of scarring.