Therapeutic effect of bone marrow mesenchymal stem cells overexpressing fibroblast growth factor on osteoporotic fracture in rats

Abstract

Objective To investigate the therapeutic effect of bone marrow mesenchymal stem cells (BMSC) overexpressing basic fibroblast growth factor (bFGF) on osteoporotic fracture in rats. Methods 80 female SD rats were randomly divided into control group, model group, BMSC group and BMSC+ bFGF group. The osteoporotic fracture model was established by resection of ovariectomized in model group, BMSC group and BMSC+ bFGF group. In group BMSC and group BMSC+ bFGF, BMSC and bFGF overexpressing BMSC were transplanted at 1, 14 and 21 d after operation respectively, while rats in the control and model groups were given the same volume of saline injection. The protein level were analyzed by Western blotting in BMSC group and BMSC+ bFGF group. Determination of bone density of rats in four group were detected by bone densitometry and fracture healing was evaluated by X-ray. The changes of bone biomechanical parameters were analyzed using three point bending test. alkaline phosphatase (ALP), runt related transcription factor-2 (Runx2) and bone morphogenetic protein-2 (BMP-2) mRNA level in four groups were analyzed by reverse transcriptase-polymerase chain reaction (RT-PCR). Results Western blot showed that the expression of bFGF factor was up-regulated in BMSC+ bFGF group. Compared with the model group [2.02±0.37, 0.051±0.002], the X-ray scores and bone mineral density significantly increased in the BMSC [3.12±0.46, 0.800±0.004] and BMSC+ bFGF groups [4.43±0.51, 0.128±0.006], and the biological parameters (maximum load, elastic load, stiffness and maximum deflection) significantly improved (P=0.032, 0.013; P=0.000, 0.000). Compared with the BMSC group, the X-ray score and bone mineral density in the BMSC+ bFGF group significantly increased (P=0.010, 0.010) and the biological parameters (maximum load, elastic load, stiffness and maximum deflection) significantly improved (P=0.002, 0.000; P=0.000, 0.000). Compared with the model group (1.41±0.19, 1.31±0.20, 1.43±0.24), the levels of ALP, Runx2 and BMP-2 mRNA in callus tissue of BMSC group (2.16±0.33, 2.48±0.31, 3.17±0.33) and BMSC+ bFGF group (4.48±0.48, 5.13±0.41, 4.89±0.49) significantly increased (P=0.000). Compared with group BMSC, the levels of ALP, Runx2 and BMP-2 mRNA in callus tissue of BMSC+ bFGF group more significantly increased (P=0.000). Conclusion Overexpression of bFGF in BMSC can increase the expression of bone morphogenetic protein, increase bone mineral density, promote the healing of osteoporotic fracture, and enhance the biological stress of fracture. Key words: Bone marrow mesenchymal stem cells; Basic fibroblast growth factor; Osteoporotic fractures; Bone mineral density; Bone healing; Biology