Regulation mechanism of BMP2 on CXCL12 expression in fracture repair and its clinical significance

KANG Kai; BAI Dong-yu; XUE Jian-li; LUAN Yan-jun; LIU Yan-xiong

doi:10.3969/j.issn.2095-252X.2017.11.009

Abstract：Objective To investigate regulation mechanism of bone morphogenic protein 2 ( BMP2 ) on chemokine C-X-C motif-ligand-12 ( CXCL12 ) expression in the fracture repair and its clinical significance. Methods Knockout mice of BMP2 ( BMP2cKO/+and BMP2cKO/cKO) were constructed. Immunohistochemistry methods were used to analyze the cells with CXCL12 expression and the timely changes in the controlled, BMP2cKO/+and BMP2cKO/cKO mice bone fracture repair models. Real time-qPCR was used to compare the expression changes of CXCL12, osteocalcin and α-SMA gene in endosteal cells and differential endosteal cells isolated from the controlled, BMP2cKO/+and BMP2cKO/cKOmice. Results The expression of BMP2 was significantly lower in BMP2cKO/+and BMP2cKO/cKOmice than the controlled mice. CXCL12 was expressed in the endosteal cells and some osteocytes during mice fracture repair, and the cells with CXCL12 expression increased at the beginning and then decreased. The endosteal cells and osteocytes which expressed CXCL12 increased gradually in BMP2cKO/+mice. CXCL12 expression in endosteal cells isolated from BMP2cKO/+mice was higher than that cells from the controlled mice. In isolated endosteal cells, rhBMP2, while inducing osteoblastic differentiation, stimulated expression of osteocalcin and α-SMA that was coupled with a decrease of CXCL12 expression significantly. In isolated BMP2cKO/cKOendosteal cells, high CXCL12 expression and low osteocalcin expression were observed. In isolated BMP2cKO/cKOendosteal cells with AMD3100 ( an antagonist of CXCL12 receptor ) treatment, osteocalcin and α-SMA expression increased. Conclusions In fracture repair process, BMP2 leads to the downregulation of CXCL12 expression that would facilitate endosteal cells differentiating into osteoblasts and promote fracture healing.