Department of Rehabilitation Medicine, Second Affiliated Hospital of Nanchang University, Nanchang City, Jiangxi Province 330008, China.
Department of Ultrasound (Musculoskeletal Ultrasound), Second Affiliated Hospital of Nanchang University, Nanchang City, Jiangxi Province 330008, China.
Comput Math Methods Med. 2022 Jul 18;2022:4487864. doi: 10.1155/2022/4487864. eCollection 2022.
In recent years, plentiful studies have uncovered the long noncoding RNA's (lncRNA's) momentous functions in osteonecrosis of the femoral head (ONFH), but the specific mechanism has not been fully illustrated. The study was to figure out lncRNA Zinc finger antisense 1 (LncZFAS1)'s biological function and its latent downstream molecular mechanism in glucocorticoid- (GC-) induced ONFH. The results manifested LncZFAS1 and transforming growth factor type III receptor (TGFBR3) were elevated, while microRNA- (miR-) 124-3p was reduced in ONFH tissues and cells. Knockdown LncZFA1 reduced rat femoral cell apoptosis, perfected bone microstructure and bone density, and accelerated osteogenic proteins bone morphogenetic protein- (BMP-) 9, BMP-3, and osteocalcin. In vitro studies manifested knockdown LncZFAS1 prevented GC-induced reduction in osteoblast advancement with facilitating osteoblast calcification capacity, ALP activity, and osteogenic proteins. Elevation of LncZFAS1 further aggravated GC-induced osteoblast injury, but this effect was turned around by enhancement of miR-124-3p or knockdown of TGFBR3. Mechanistically, LncZFAS1 performed as a sponge for miR-124-3p to mediate TGFBR3 expression to motivate GC-induced ONFH. All in all, the results of this study indicate the LncZFAS1/miR-124-3p/TGFBR3 axis is supposed to be a latent therapeutic molecular target for GC-induced ONFH.
近年来，大量研究揭示了长非编码 RNA（lncRNA）在股骨头坏死（ONFH）中的重要作用，但具体机制尚未完全阐明。本研究旨在探讨 lncRNA 锌指反义 1（LncZFAS1）在糖皮质激素（GC）诱导的 ONFH 中的生物学功能及其潜在的下游分子机制。结果表明，ONFH 组织和细胞中 LncZFAS1 和转化生长因子型 III 受体（TGFBR3）升高，而 microRNA-（miR-）124-3p 降低。敲低 LncZFA1 减少大鼠股骨细胞凋亡，改善骨微结构和骨密度，加速成骨蛋白骨形态发生蛋白-（BMP-）9、BMP-3 和骨钙素的表达。体外研究表明，敲低 LncZFAS1 可防止 GC 诱导的成骨细胞减少，同时促进成骨细胞钙化能力、碱性磷酸酶（ALP）活性和成骨蛋白的表达。LncZFAS1 的升高进一步加重了 GC 诱导的成骨细胞损伤，但通过增强 miR-124-3p 或敲低 TGFBR3 可以逆转这种效应。机制上，LncZFAS1 作为 miR-124-3p 的海绵体来调节 TGFBR3 的表达，从而促进 GC 诱导的 ONFH。总之，本研究结果表明，LncZFAS1/miR-124-3p/TGFBR3 轴可能是 GC 诱导的 ONFH 的潜在治疗分子靶点。
