Overexpression of HIF-1alpha in Bone Marrow Mesenchymal Stem Cells Promote the Repair of Mandibular Condylar Osteochondral Defect in a Rabbit Model

Abstract

The self-repair ability of temporomandibular joint (TMJ) cartilage is limited. Hypoxia-inducible factor-1 alpha (HIF-1alpha) may induce stem cells to promote chondrogenic repair. The purpose of this study was to systematically evaluate the effect of HIF-1alpha overexpression in bone marrow mesenchymal stem cells (BMSCs) combined with collagen scaffolds on the repair of TMJ condylar osteochondral defects in a rabbit model. Osteochondral defects of 3-mm diameter×2-mm depth were created at the right side of the mandibular condyle in 40 New Zealand white rabbits. The defect sites were treated with simple empty, collagen scaffolds (COL), BMSCs/COL, and HIF-1alpha overexpression BMSCs/COL groups. The histomorphologic features of condylar cartilage were monitored by gross examination, safranin O-fast green staining (Solarbio, Beijing, China), and immunohistochemical staining. The changes in subchondral bone were examined by microcomputed tomography. Immunofluorescence staining was used to trace the transplanted BMSCs invivo. At 12weeks postimplantation, histologic staining showed that the osteochondral defects in the simple empty and COL groups were mainly filled with fibrous tissue, whereas the BMSCs/COL and HIF-1alpha overexpression BMSCs/COL groups repaired the defect with fibrocartilage. Furthermore, the cartilage was better organized in the HIF-1alpha overexpression BMSCs/COL group compared with the BMSCs/COL group. Microcomputed tomography showed that osteochondral defects can cause abnormal hyperosteogeny in subchondral bone, and the transplantation of BMSCs, especially HIF-1alpha overexpression BMSCs, may alleviate osteosclerosis. Immunofluorescence staining showed that HIF-1alpha overexpression can promote the survival of transplanted BMSCs. The transplantation of HIF-1alpha overexpression BMSCs combined with a COL scaffold promotes cartilaginous repair of condylar cartilage and inhibits subchondral bone sclerosis in TMJ condylar osteochondral defect rabbits.