Overexpression of Pitx1 attenuates the senescence of chondrocytes from osteoarthritis degeneration cartilage–A self-controlled model for studying the etiology and treatment of osteoarthritis

Abstract To explore the role of low expression of Pitx1 in degenerative cartilage tissue. A cartilage injury model was established by using the cartilage scratch method. The newly generated tissue by BrdU labeled in injured cartilage region expressed SOX-9 and Col2A1 in 5-week-old rats. Compared with that, the number of BrdU-positive cells was lower in 4-month-old cartilage injury model rats. Compared with that in lateral cartilage, the expression of Pitx1 was lower in medial cartilage. Compared with chondrocytes derived from the lateral cartilage, chondrocytes derived from the medial cartilage exhibited significantly increased cell aging, as determined by SA-β-GAL staining; downregulated Pitx1 expression; reduced autophagy levels; and decreased Col2A1 expression in a chondrogenic differentiation assay. Inhibition of Pitx1 expression in chondrocytes from the lateral cartilage significantly increased the ratio of cell senescence. Overexpression of Pitx1 in chondrocytes derived from the medial cartilage decreased the cell senescence ratio. In a luciferase assay, Pitx1 was found to promote Sirt1 gene transcription. Decreased Pitx1 expression is an essential cause of cartilage degeneration in the medial tibial plateau. The described self-controlled model is an excellent way to study OA etiology and screen therapeutic drugs for OA.