Abstract
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.
Highlights
Osteoporosis is one of the most common bone diseases with bone loss and reduced bone mineral density (BMD), which increases bone fragility and occurrence of fracture[1]
After induction for 0, 7, and 14 days, the osteogenic capabilities of hBMSCs were evaluated by alkaline phosphatase (ALP) staining and ALP activity assay for osteoblast differentiation, Alizarin red S staining, and quantification for calcium mineralization
These data hinted that circ-itchy E3 ubiquitin-protein ligase (ITCH), miR-214, and yes-associated protein 1 (YAP1) may be involved in osteogenic differentiation of osteoporosis
Summary
Osteoporosis is one of the most common bone diseases with bone loss and reduced bone mineral density (BMD), which increases bone fragility and occurrence of fracture[1]. Osteoporotic fracture usually results in lasting disability and mortality in the elderly population and postmenopausal women[2]. In China, it is predicted that at least 90 million people suffer from osteoporosis[3]. Because of the high prevalence rate, there is a great demand to find effective methods of osteoporosis prevention and treatment. Studies have shown that in people with osteoporosis, bone loss is induced by the reduced bone formation and increased bone resorption[4,5]. The bone formation could be modulated by many transcription
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