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

Stem Cell Research & Therapy

Yunfei Yang¹  Chengjie Lian²  Weiqian Jiang²  Yu Chen²  Minkang Guo²  Wu Yang²  Haobo Bai²  Jian Zhang²  Zijie Xu²  Weiwen Zhu³  Tingmei Chen⁴  Husun Qian⁴ 

[1]Department of Geriatrics, The First Affiliated Hospital of Chongqing Medical University, 400016, Chongqing, China

[2]Department of Orthopedics, The First Affiliated Hospital of Chongqing Medical University, 400016, Chongqing, China

[3]Department of Orthopedics, The First Affiliated Hospital of Sun Yat-sen University, 510080, Guangzhou, China

[4]Key Laboratory of Diagnostic Medicine Designated by the Ministry of Education, Chongqing Medical University, 400016, Chongqing, China

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

DOI  :  10.1186/s13287-021-02438-y

来源: Springer

【 摘 要 】

BackgroundNontraumatic 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.MethodsRT-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.ResultsThe 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.ConclusionThe 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).

【 授权许可】

CC BY