Tgif1 and SnoN modified chondrocytes or stem cells for tendon-bone insertion regeneration

Tendon-bone insertion injuries are a common occurrence but rarely heal, despite the many strategies that have been employed. The tendon-bone insertion consists of four types of tissues: tendon, fibrocartilage, mineral fibrocartilage and bone, making it hard to regenerate. The key to reconstructing the tendon enthesis is to rebuild the gradations of cell type, collagen type, mineral content and collagen fiber orientation. Chondrocytes were found to be able to differentiate into tendon and bone tissues upon special stimulation, which offers promise for tendon enthesis regeneration. Tgif1 is a key factor that represses the expression of the cartilage master gene Sox9, which is induced by TGFβs, and changes the expression rate of Sox9 versus Scx, eventually promoting fibrogenesis. SnoN is a key factor that is induced by TGFβs to inhibit the hypertrophy of chondrocytes and therefore bone formation. It appears that the induction of Tgif1 and the repression of SnoN can cause chondrocytes to differentiate into tendon and bone tissues. Moreover, a gradation of the expression levels of Tgif1 and SnoN in chondrocytes may create a gradation of the tissue from tendon to fibrocartilage to bone. Consequently, we propose that a gradation of gene-modified chondrocytes (Tgif1-inducing cells, primary cells, SnoN-repressing cells) or stem cells that arise from a gradation of stimulation (Tgif1 induction and SnoN repression) will aid in the regeneration of the tendon-bone insertion.