Department of Orthopaedics, Xiangya Hospital of Central South University, 410008, Changsha, Hunan Province, People's Republic of China.
Hunan Key Laboratory of Aging Biology, Xiangya Hospital, Central South University, 410008, Changsha, Hunan Province, People's Republic of China.
Cell Death Dis. 2021 Apr 1;12(4):340. doi: 10.1038/s41419-021-03586-y.
Osteoporosis is the most prevailing primary bone disease and a growing health care burden. The aim of this study was to clarify the functional roles and mechanisms of the circ-ITCH regulating osteogenic differentiation of osteoporosis. Circ-ITCH and yes-associated protein 1 (YAP1) levels were downregulated, but the miR-214 level was upregulated in osteoporotic mice and patients. Knockdown of circ-ITCH inhibited the alkaline phosphatase (ALP) activity, mineralized nodule formation, and expression of runt-related transcription factor 2 (RUNX2), osteopontin (OPN), and osteocalcin (OCN) during osteogenic induction. Furthermore, miR-214 was a target of circ-ITCH, knockdown of miR-214 could impede the regulatory effects of sh-circ-ITCH on osteogenic differentiation. Moreover, miR-214 suppressed hBMSCs osteogenic differentiation by downregulating YAP1. Finally, in vivo experiments indicated that overexpression of circ-ITCH could improve osteogenesis in ovariectomized mice. In conclusion, circ-ITCH upregulated YAP1 expression to promote osteogenic differentiation in osteoporosis via sponging miR-214. Circ-ITCH could act as a novel therapeutic target for osteoporosis.
骨质疏松症是最常见的原发性骨病，也是日益加重的医疗保健负担。本研究旨在阐明 circ-ITCH 在调控骨质疏松症成骨分化中的功能作用和机制。骨质疏松症小鼠和患者的 circ-ITCH 和 yes 相关蛋白 1（YAP1）水平下调，而 miR-214 水平上调。circ-ITCH 敲低抑制碱性磷酸酶（ALP）活性、矿化结节形成以及成骨诱导过程中 runt 相关转录因子 2（RUNX2）、骨桥蛋白（OPN）和骨钙素（OCN）的表达。此外，miR-214 是 circ-ITCH 的靶标，miR-214 的敲低可阻碍 sh-circ-ITCH 对成骨分化的调节作用。此外，miR-214 通过下调 YAP1 抑制 hBMSCs 成骨分化。最后，体内实验表明过表达 circ-ITCH 可改善去卵巢小鼠的成骨作用。总之，circ-ITCH 通过海绵吸附 miR-214 上调 YAP1 表达促进骨质疏松症成骨分化。circ-ITCH 可以作为骨质疏松症的一种新的治疗靶点。
