Jiang Xiaowei, Wang Qiang, Ying Pu, Jiang Wentao, Qian Zhiyuan, Lu Wei
Department of Orthopaedic, Changshu Hospital Affiliated to Nanjing University of Chinese Medicine, Changshu, Jiangsu, China.
Department of Orthopaedic, Changshu Hospital Affiliated to Nanjing University of Chinese Medicine, Changshu, Jiangsu, China
Ann Clin Lab Sci. 2025 Mar;55(2):231-239.
Osteoporosis is a common disorder marked by bone loss, fragility, and fractures. microRNAs (miRNAs) are highlighted as potential regulators of osteoblast differentiation, and exosomes carrying miRNAs from bone marrow stromal cells (BMSCs) are applied to treatment. Herein, we aimed to clarify the role of miR-17 and BMSCs in ovariectomized rats with osteoporosis.
After establishment of an osteoporosis animal model, miR-17 and BARX2 expression in ovariectomized rat tissues and osteoblasts were detected. Osteoblasts were transfected with mimics and inhibitor and co-cultured with BMSCs, whilst cell proliferation and differentiation were evaluated.
miR-17 was poorly expressed in ovariectomized rat tissue, while BARX2 was up-regulated. Overexpression of miR-17 induced decreased BARX2 expression but enhanced proliferation and differentiation of osteoblasts in osteoporotic rats. Importantly, the presence of BMSCs also facilitated osteoblast differentiation and decreased BARX2 expression, which was abolished by addition of exosome inhibitors. Mechanistically, miR-17 targeted BARX2 expression to up-regulate ALP and Co1-I in osteoporosis.
Collectively, miR-17 delivered by BMSC exosomes promotes osteogenic differentiation and induces bone healing in osteoporosis through BARX2 regulation. The combined use of exosome inhibitors confirmed the therapeutic effect of BMSCs and BMSC exosomes containing miRNAs on various diseases.
骨质疏松症是一种以骨质流失、骨脆性增加和骨折为特征的常见疾病。微小RNA(miRNA)被认为是成骨细胞分化的潜在调节因子,携带miRNA的骨髓间充质干细胞(BMSC)来源的外泌体已被应用于治疗。在此,我们旨在阐明miR-17和BMSC在去卵巢骨质疏松大鼠中的作用。
建立骨质疏松动物模型后,检测去卵巢大鼠组织和成骨细胞中miR-17和BARX2的表达。用模拟物和抑制剂转染成骨细胞,并与BMSC共培养,同时评估细胞增殖和分化。
miR-17在去卵巢大鼠组织中表达较低,而BARX2上调。miR-17的过表达导致BARX2表达降低,但增强了骨质疏松大鼠成骨细胞的增殖和分化。重要的是,BMSC的存在也促进了成骨细胞分化并降低了BARX2表达,而外泌体抑制剂的加入消除了这种作用。机制上,miR-17靶向BARX2表达以上调骨质疏松症中的碱性磷酸酶(ALP)和I型胶原蛋白(Co1-I)。
总体而言,BMSC来源的外泌体携带的miR-17通过调节BARX2促进骨质疏松症中的成骨分化并诱导骨愈合。外泌体抑制剂的联合使用证实了BMSC和含有miRNA的BMSC外泌体对各种疾病的治疗作用。