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Cell Death Dis ; 12(4): 340, 2021 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-33795657

RESUMEN

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.


Asunto(s)
Proteínas Adaptadoras Transductoras de Señales/metabolismo , Diferenciación Celular/fisiología , MicroARNs/metabolismo , Osteoporosis/metabolismo , Factores de Transcripción/metabolismo , Animales , Células Cultivadas , Humanos , Células Madre Mesenquimatosas/metabolismo , Ratones , MicroARNs/genética , Osteoblastos/metabolismo , Osteogénesis/genética , Osteogénesis/fisiología , Proteínas Señalizadoras YAP
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