Stromal Cell-Derived Factor-1 Accelerates Cartilage Defect Repairing by Recruiting Bone Marrow Mesenchymal Stem Cells and Promoting Chondrogenic Differentiation

摘要

Chemokine stromal cell-derived factor-1 (SDF-1) is a powerful chemoattractant for the localization of CXCR4-positive bone marrow mesenchymal stem cells (BMSCs) into the bone marrow. We studied the effects of SDF-1 on the cartilage defect repair by recruiting BMSCs and promoting its chondrogenic differentiation in vitro and in vivo. Chemotaxis analysis with Transwell plate showed that SDF-1 could recruit BMSCs through SDF-1/CXCR4 axis. Real-time polymerase chain reaction, enzyme-linked immunosorbent assays, and Western blot results suggested that the levels of type II collagen and GAG were increased after incubating BMSCs with SDF-1 compared with the without SDF-1 group. More positive BrdU-labeled BMSCs were detected at the cartilage defect region in the SDF-1 + poly [lactide-co-glycolide] (PLGA) scaffold group (SP) in which those animals showed a smooth and transparent cartilage tissue with a strong staining of toluidine blue and type II collagen compared with the no-SDF-1 groups. ICRS score suggested that the repair effect in the SDF-1 + PLGA-treated animals was improved compared with PLGA scaffold group alone at 4 and 8 weeks after surgery; the repair effect from the SDF + PLGA-treated animals was significantly improved compared with the PLGA alone at 12 weeks after surgery. Our in vitro and in vivo results indicated the following: (1) SDF-1 could recruit the BMSCs into cartilage defect area. (2) SDF-1 induces BMSCs expressing type II collagen and GAG, which may accelerate the BMSCs transforming into chondrocytes under the cartilage microenvironment in vivo. (3) PLGA scaffold attached with SDF-1 remarkably promoted the cartilage defect repairing. The defected cartilage was filled with transparent cartilage 12 weeks after the surgery, which shared a similar structure with the adjacent normal cartilage. Taken together, this research provides a new strategy for cartilage defect repairing.