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J Cell Mol Med ; 24(21): 12619-12632, 2020 11.
Artículo en Inglés | MEDLINE | ID: mdl-32975015

RESUMEN

MicroRNAs (miRNAs) have been corroborated to engage in the process of cellular activities in osteoporosis. However, few researches have been conducted to expose the integrated role of miR-497, leucine-rich alpha-2-glycoprotein-1 (LRG1) and transforming growth factor beta 1 (TGF-ß1)/Smads signalling pathway in osteoporosis. Thereafter, the study is set out to delve into miR-497/LRG1/TGF-ß1/Smads signalling pathway axis in osteoporosis. Osteoporosis bone tissues and normal bone tissues were collected. Rat osteoporosis models were constructed via ovariectomy. Model rats were injected with restored miR-497 or depleted LRG1 to explore their roles in osteoporosis. Rat osteoblasts were extracted from osteoporosis rats and transfected with restored miR-497 or depleted LRG1 for further verification. MiR-497 and LRG1 expression in femoral head tissues and osteoblasts of osteoporosis rats were detected. TGF-ß1/Smads signalling pathway-related factors were detected. MiR-497 was poorly expressed while LRG1 was highly expressed and TGF-ß1/Smads signalling pathway activation was inhibited in osteoporosis. MiR-497 up-regulation or LRG1 down-regulation activated TGF-ß1/Smads signalling pathway, promoted collagen type 1 synthesis and suppressed oxidative stress in femoral head tissues in osteoporosis. MiR-497 restoration or LRG1 knockdown activated TGF-ß1/Smads signalling pathway, promoted viability and suppressed apoptosis of osteoblasts in osteoporosis. Our study suggests that miR-497 up-regulation or LRG1 down-regulation promotes osteoblast viability and collagen synthesis via activating TGF-ß1/Smads signalling pathway, which may provide a novel reference for osteoporosis treatment.


Asunto(s)
Colágeno/biosíntesis , Glicoproteínas/metabolismo , MicroARNs/metabolismo , Osteoblastos/patología , Osteoporosis/metabolismo , Osteoporosis/patología , Proteínas Smad/metabolismo , Factor de Crecimiento Transformador beta1/metabolismo , Fosfatasa Alcalina/metabolismo , Animales , Apoptosis , Biomarcadores/metabolismo , Calcio/sangre , Calcio/orina , Supervivencia Celular , Regulación hacia Abajo/genética , Femenino , Cabeza Femoral/patología , Regulación de la Expresión Génica , Técnicas de Silenciamiento del Gen , Glicoproteínas/genética , Hidroxiprolina/metabolismo , MicroARNs/genética , Modelos Biológicos , Osteoblastos/metabolismo , Estrés Oxidativo , Fósforo/sangre , Fósforo/orina , Ratas Sprague-Dawley , Transducción de Señal , Regulación hacia Arriba/genética
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