血管内皮生长因子
脂肪生成
血管生成
MAPK/ERK通路
间充质干细胞
血管内皮生长因子A
细胞生物学
化学
分子生物学
癌症研究
生物
激酶
血管内皮生长因子受体
作者
Hongliang Wu,Chen Guo-cheng,Guibao Zhang,Qiang Lu,Gu Di,Minhua Dai
标识
DOI:10.1088/1748-605x/acb412
摘要
Steroid-induced avascular necrosis of the femoral head (SANFH) is an intractable orthopedic disease. This study investigated the regulatory effect and molecular mechanism of vascular endothelial cell (VEC)-derived exosomes (Exos) modified with vascular endothelial growth factor (VEGF) in osteogenic and adipogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) in SANFH. VECs were culturedin vitroand transfected with adenovirus Adv-VEGF plasmids. Exos were extracted and identified.In vitro/vivoSANFH models were established and treated with VEGF-modified VEC-Exos (VEGF-VEC-Exos). The internalization of Exos by BMSCs, proliferation and osteogenic and adipogenic differentiation of BMSCs were determined by the uptake test, cell counting kit-8 (CCK-8) assay, alizarin red staining, and oil red O staining. Meanwhile, the mRNA level of VEGF, the appearance of the femoral head, and histological analysis were assessed by reverse transcription quantitative polymerase chain reaction and hematoxylin-eosin staining. Moreover, the protein levels of VEGF, osteogenic markers, adipogenic markers, and mitogen-activated protein kinase (MAPK)/extracellular regulated protein kinases (ERK) pathway-related indicators were examined by Western blotting, along with evaluation of the VEGF levels in femur tissues by immunohistochemistry. Glucocorticoid (GC) induced adipogenic differentiation of BMSCs and inhibited osteogenic differentiation. VEGF-VEC-Exos accelerated the osteogenic differentiation of GC-induced BMSCs and inhibited adipogenic differentiation. VEGF-VEC-Exos activated the MAPK/ERK pathway in GC-induced BMSCs. VEGF-VEC-Exos promoted osteoblast differentiation and suppressed adipogenic differentiation of BMSCs by activating the MAPK/ERK pathway. VEGF-VEC-Exos accelerated bone formation and restrained adipogenesis in SANFH rats. VEGF-VEC-Exos carried VEGF into BMSCs and motivated the MAPK/ERK pathway, thereby promoting osteoblast differentiation of BMSCs in SANFH, inhibiting adipogenic differentiation, and alleviating SANFH.
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