Exosomal miR-100-5p inhibits osteogenesis of hBMSCs and angiogenesis of HUVECs by suppressing the BMPR2/Smad1/5/9 signalling pathway

作者全名："Yang, Wu; Zhu, Weiwen; Yang, Yunfei; Guo, Minkang; Qian, Husun; Jiang, Weiqian; Chen, Yu; Lian, Chengjie; Xu, Zijie; Bai, Haobo; Chen, Tingmei; Zhang, Jian"

作者地址："[Yang, Wu; Guo, Minkang; Jiang, Weiqian; Chen, Yu; Lian, Chengjie; Xu, Zijie; Bai, Haobo; Zhang, Jian] Chongqing Med Univ, Affiliated Hosp 1, Dept Orthoped, Chongqing 400016, Peoples R China; [Qian, Husun; Chen, Tingmei] Chongqing Med Univ, Minist Educ, Key Lab Diagnost Med Designated, Chongqing 400016, Peoples R China; [Yang, Yunfei] Chongqing Med Univ, Affiliated Hosp 1, Dept Geriatr, Chongqing 400016, Peoples R China; [Zhu, Weiwen] Sun Yat Sen Univ, Affiliated Hosp 1, Dept Orthoped, Guangzhou 510080, Peoples R China"

通信作者："Zhang, J (corresponding author), Chongqing Med Univ, Affiliated Hosp 1, Dept Orthoped, Chongqing 400016, Peoples R China."

来源：STEM CELL RESEARCH & THERAPY

ESI学科分类：MOLECULAR BIOLOGY & GENETICS

WOS号：WOS:000675242000014

JCR分区：Q1

影响因子：7.5

年份：2021

卷号：12

期号：1

开始页：　

结束页：　

文献类型：Article

关键词：Nontraumatic osteonecrosis of the femoral head; NONFH; Exosomes; Osteogenic differentiation; Adipocyte differentiation; Angiogenesis; miRNAs; BMPR2; miR-100-5p

摘要："Background Nontraumatic osteonecrosis of the femoral head (NONFH) is a common, progressive, and refractory orthopaedic disease. Decreased osteogenesis and angiogenesis are considered the main factors in the pathogenesis of NONFH. We aimed to figure out whether exosomes and exosomal miRNA from necrotic bone tissues of patients with NONFH are involved in the pathogenesis of NONFH and reveal the underlying mechanisms. Methods RT-PCR and western blotting (WB) were used to detect the expression of osteogenic, adipogenic, and angiogenic markers. ALP staining and Alizarin Red S (ARS) staining were used to evaluate osteogenic differentiation of human bone marrow-derived mesenchymal stem cells (hBMSCs). Oil Red O staining was performed to assess the adipocyte deposition. A tube formation assay was used to study angiogenesis of human umbilical vascular endothelial cells (HUVECs). H&E staining and immunohistochemistry (IHC) staining were used to detect the effect of the NONFH exosomes in vivo. MicroRNA sequencing was conducted to identify potential regulators in the NONFH exosomes. The target relationship between miR-100-5p and BMPR2 was predicted and confirmed by a dual luciferase reporter assay and WB. Results The NONFH exosomes reduced the osteogenic differentiation of hBMSCs and angiogenesis of HUVECs. In addition, the injection of the NONFH exosomes caused thinning and disruption of bone trabeculae in the femoral heads of rats. MiR-100-5p expression was upregulated in the NONFH exosomes and inhibited the osteogenesis of hBMSCs and angiogenesis of HUVECs by targeting BMPR2 and suppressing the BMPR2/SMAD1/5/9 signalling pathway. Silencing miR-100-5p expression rescued the reduction in osteogenesis and angiogenesis caused by the NONFH exosomes by activating the BMPR2/SMAD1/5/9 signalling pathway. Conclusion The NONFH exosomal miR-100-5p can lead to NONFH-like damage by targeting BMPR2 and suppressing the BMPR2/SMAD1/5/9 signalling pathway, which may be involved in the pathophysiological mechanisms of nontraumatic osteonecrosis of the femoral head (NONFH)."

基金机构：Medical Research Project of Health and Family Planning Commission in Chongqing [2017ZDXM006]; General Project of Technology Innovation and Application Development of Chongqing Science and Technology Bureau [cstc2019jscxmsxmX0245]

基金资助正文：This work was funded by Medical Research Project of Health and Family Planning Commission in Chongqing (Grant No. 2017ZDXM006) and General Project of Technology Innovation and Application Development of Chongqing Science and Technology Bureau (Grant No. cstc2019jscxmsxmX0245).