Yin Yukun, Ding Lixiang, Hou Yu, Jiang Haoran, Zhang Ji, Dai Zhong, Zhang Genai
Department of Traditional Chinese Medicine, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China.
Department of Spine, Beijing Shijitan Hospital, Capital Medical University, No.10 Tieyi Road, Yangfangdian, Haidian District, Beijing, 100038, People's Republic of China.
Nanoscale Res Lett. 2019 Dec 18;14(1):383. doi: 10.1186/s11671-019-3221-6.
Little is known regarding the functional role of microRNA-410 (miR-410) in osteonecrosis of the femoral head (ONFH); hence, the aim of the present study was to investigate miR-410 targeting Wnt-11 to modulate the osteogenic and osteoclastic mechanism in the prevention of ONFH.
Fifteen ONFH samples and 15 normal samples were gathered. The pathological changes of the femoral head, osteoblasts, and osteoclasts in the clinical samples were observed. The rat model of ONFH was injected with agomir-miR-410, Wnt-11-siRNA, or oe-Wnt-11. MiR-410; Wnt-11; osteoblast-related factors alkaline phosphatase (ALP), bone gamma-carboxyglutamate protein (BGLAP), and Collα1 expression; and osteoclast-related factors acid phosphatase 5 (ACP5), cathepsin K (CTSK), and MMP9, as well as Bcl-2 and Bax expression, were tested by RT-qPCR and western blot analysis. The osteogenic function index ALP and OCN together with osteoclast function index NTX-1 and CTX-1 in serum was tested by ELISA.
MiR-410, ALP, BGLAP, and Collα1 degraded as well as Wnt-11, ACP5, CTSK, and MMP9 enhanced in ONFH tissues of the clinical samples. Upregulated miR-410 and downregulated Wnt-11 enhanced bone mineral density (BMD) and BV/TV of rats, heightened the BMD level of the femoral shaft, femoral head, and spinal column, and also raised the serum calcium and phosphorus levels of rats, while restrained apoptosis of osteocytes, elevated OCN, ALP, BGLAP, and Collα1 expression and declined ACP5, CTSK, NTX-1, CTX-1, and MMP9 expression in rats.
This study suggested that upregulating miR-410 or downregulating Wnt-11 increases osteoblasts and reduces osteoclasts to alleviate the occurrence of ONFH. Thus, miR-410 may serve as a potential target for the treatment of ONFH.
关于微小RNA - 410（miR - 410）在股骨头坏死（ONFH）中的功能作用知之甚少；因此，本研究的目的是探讨miR - 410靶向Wnt - 11以调节成骨和破骨机制来预防ONFH。
收集15例ONFH样本和15例正常样本。观察临床样本中股骨头、成骨细胞和破骨细胞的病理变化。将agomir - miR - 410、Wnt - 11 - siRNA或oe - Wnt - 11注射到ONFH大鼠模型中。通过RT - qPCR和蛋白质免疫印迹分析检测miR - 410、Wnt - 11、成骨细胞相关因子碱性磷酸酶（ALP）、骨钙素（BGLAP）和Ⅰ型胶原蛋白（Collα1）的表达；破骨细胞相关因子酸性磷酸酶5（ACP5）、组织蛋白酶K（CTSK）和基质金属蛋白酶9（MMP9），以及Bcl - 2和Bax的表达。通过酶联免疫吸附测定（ELISA）检测血清中成骨功能指标ALP和骨钙素（OCN）以及破骨细胞功能指标交联I型胶原C端肽（NTX - 1）和交联I型胶原N端肽（CTX - 1）。
临床样本的ONFH组织中miR - 410、ALP、BGLAP和Collα1降解，而Wnt - 11、ACP5、CTSK和MMP9增强。上调miR - 41且下调Wnt - 11可提高大鼠的骨密度（BMD）和骨体积分数（BV/TV），提高大鼠股骨干、股骨头和脊柱的BMD水平，还可提高大鼠血清钙和磷水平，同时抑制骨细胞凋亡，提高大鼠体内OCN、ALP、BGLAP和Collα1的表达，降低ACP5、CTSK、NTX - 1、CTX - 1和MMP9的表达。
本研究表明，上调miR - 410或下调Wnt - 11可增加成骨细胞并减少破骨细胞，以减轻ONFH的发生。因此，miR - 410可能成为治疗ONFH的潜在靶点。
