Roles of TGF-β in the therapeutic potential of hypoxic mesenchymal stem cells for treating osteoarthritis in a Rabbit model.

Abstract

BACKGROUND: Osteoarthritis (OA) is the most prevalent musculoskeletal disease worldwide. Cell-based therapies have emerged as a promising approach for OA therapy. The therapeutic potential of mesenchymal stem cells (MSCs) has been demonstrated in a wide array of inflammatory diseases. A previous study demonstrated that the injection of the allogeneic MSCs cultured under hypoxia could reduce the progression of osteoarthritis in an anterior cruciate ligament transection (ACLT) model of OA in rabbits. The possible factors involved in the therapeutic effect of hypoxic MSCs in OA were further analyzed in the current study. METHODS: Using the ACLT model of OA, we investigated gene expression changes in the groups of control, OA, and OA treated by hyaluronic acid (OA + HA), and additionally injected with hypoxic MSCs (OA + HA + MSC) by PCR array. RESULTS: Increased expression of TGF-β in the group treated with hypoxic MSCs was observed. Significant higher transcript and protein expressions of TGF-β were also demonstrated in cartilage treated with hypoxic MSCs. We further generated TGF-β-knockout (KO) MSCs and observed notably reduced levels of TGF-β in cartilage treated with hypoxic TGF-β KO MSCs. Immunohistochemical analysis revealed that the group treated with TGF-β KO MSCs exhibited significantly decreased type II collagen (COL II) and increased type X collagen (COL X) as compared to that treated with MSCs without TGF-β-KO. CONCLUSIONS: Collectively, we suggest hypoxic MSCs might exert therapeutic effects mediated by stimulating TGF-β and subsequently promote and inhibit the expressions of COL II and COL X respectively.