伤科九味健骨片通过调控基质细胞衍生因子-1α/C-X-C趋化因子受体4型轴对骨髓间充质干细胞成骨分化及牵张成骨的影响OA

Objective To explore the effects of the Bushen Huoxue traditional Chinese medicine,the com-pound Shangke Jiuwei Jiangu tablet,on bone healing in the distraction osteogenesis model,and to preliminarily expound its action mechanism at the molecular and cellular levels.Methods The tibial distraction osteogenesis models of rabbits were constructed and then randomly divided into a control group,a low-dose traditional Chinese medicine(TCM)group,a medium-dose TCM group,and a high-dose TCM group.After the intervention,the morphology of the bone callus was evaluated through Micro-CT scanning and three-dimensional reconstruction,and the bone volume fraction(BV/TV)and bone mineral density(BMD)were calculated.HE staining was carried out on tissue sections to observe the histological structure of the callus.In the in-vitro experiment,the effects of drug serum on the migration ability of bone marrow mesenchymal stem cells(MSCs)were detected using the Transwell assay.The tendency of cell directional differentiation was evaluated through osteogenic/adipogenic induction differ-entiation experiments.The expression levels of Sdf-1,Cxcr4,Runx2,and Ocn mRNA in MSCs were detected by RT-PCR.Results Compared with the control group,Micro-CT revealed that the width of the fracture line decreased and the number of calluses increased in all TCM groups.The effect was most significant in the high-dose group,where continuous calluses were observed and the fracture line basically disappeared.BV/TV and BMD detection indicated that the bone healing indexes were significantly improved in the TCM groups(P<0.05),showing a dose-dependent relationship.Histological examination showed that the callus maturity was the highest in the high-dose group,and the transformation from braided bone to lamellar bone was active.In the in-vitro experiment,the migration rate of MSCs was significantly increased in the drug serum group(P<0.000 1).Osteogenic differentiation was enhanced while adipogenic differentiation was inhibited,and the expressions of Sdf-1,Cxcr4,Runx2,and Ocn mRNA were all significantly up-regulated(P<0.000 1).Conclusions Shangke Jiuwei Jiangu tablets may promote the migration of MSCs by activating the Sdf-1/Cxcr4 signaling axis and induce their osteogenic differentiation.Consequently,this can promote the formation,mineralization,and maturation of new bones during the distraction osteogenesis process both in vivo and in vitro.Its mechanism of action highly aligns with the Bushen Huoxue Jiangu method in TCM.