gms | German Medical Science

Objectives: Angiogenesis-osteogenesis couple plays a pivotal role in osteonecrosis of femoral head (ONFH) for necrosis absorption and bone remodeling. The property repair function of angiogenesis in the necrosis microenvironment is considered to depend on intercellular cross-talks under angiogenesis factors modulation.

Methods: In this study, transfected EGFL8 COS-7 was used to measure the express of lysates and supernatant. ONFH rat model and patients, confirmed by micro-computed tomography (micro-CT) and histopathological examination, was used to evaluate the expression of EGFL8. Endothelial cell (SVEC) culture was used to examine the inhibitory effect of EGFL8 on vascular formation and SVEC migration. Real time PCR was employed to examine the effect of EGFL8 on the expression of osteoclast and osteoblast, the maker genes expression in micro-fracture model. The activities of JNK/p38/ERK and Akt was analyzed by Western blotting.

Results and Conclusion: In this study, we showed that the modulated function of EGF-like domain 8 (EGFL8), a member of epidermal growth factor (EGF) repeat protein superfamily in ONFH. As advanced reports, it is expressed in osteoblast lineages, and promotes endothelial cell activities. The protein expression of EGFL8 is significantly increased in vivo, the osteonecrosis sample of steroid-induce ONFH rat model. Also, high expression of EGFL8, both of gene and protein were seen in necrosis area (micro-fracture) of ONFH patients, followed by the penumbra and normal area. Addition of EGFL8 highly strengthen SVEC migration, promotes tube-like structure formation in vitro. As for signaling modulation analysis, results show that EGFL8 induces the phosphorylation of MAPK/ERK. In summary, our results demonstrate that EGFL8 expressed by osteoblasts and osteoclasts improves endothelial cell activities through integrin-mediated signaling. The study highlights the important role of EGFL8 in osteonecrosis of femoral head for regulating the angiogenesis of bone repair.