4.7 Article

LncRNA MALAT1 mediates osteogenic differentiation in osteoporosis by regulating the miR-485-5p/WNT7B axis

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FRONTIERS IN ENDOCRINOLOGY
卷 13, 期 -, 页码 -

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FRONTIERS MEDIA SA
DOI: 10.3389/fendo.2022.922560

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osteoporosis; MALAT1; WNT7B; osteogenesis differentiation; MiR-485-5p

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This study investigates the role of MALAT1 in osteogenic differentiation and cell apoptosis in osteoporosis. MALAT1 upregulates the expression of Bmp4, Col1a1, and Spp1, enhances ALP activity, and inhibits apoptosis. MALAT1 promotes osteogenic differentiation and inhibits cell apoptosis through the miR-485-5p/WNT7B axis, suggesting its potential as a target for alleviating osteoporosis.
IntroductionAccumulating evidence demonstrates that long non-coding RNAs (lncRNAs) are associated with the development of osteoporosis. MethodsThis study aimed to investigate the effects of MALAT1 on osteogenic differentiation and cell apoptosis in osteoporosis. MALAT1 level, detected by RT-qPCR, was downregulated in hindlimb unloading (HU) mice and simulated microgravity (MG)-treated MC3T3-E1 cells. Moreover, osteogenic differentiation-related factor (Bmp4, Col1a1, and Spp1) levels were measured by RT-qPCR and Western blot. ALP activity was detected, and ALP staining was performed. Cell apoptosis was assessed by flow cytometry. ResultsThe results revealed that MALAT1 upregulated the expression of Bmp4, Col1a1, and Spp1, and enhanced ALP activity. Knockdown of MALAT1 suppressed their expression and ALP activity, suggesting that MALAT1 promoted osteogenic differentiation. Additionally, MALAT1 inhibited apoptosis, increased Bax and caspase-3 levels, and decreased Bcl-2 level. However, knockdown of MALAT1 had opposite results. In MG cells, MALAT1 facilitated osteogenic differentiation and suppressed apoptosis. Furthermore, miR-485-5p was identified as a target of MALAT1, and WNT7B was verified as a target of miR-485-5p. Overexpression of miR-485-5p rescued the promotion of osteogenic differentiation and the inhibition of apoptosis induced by MALAT1. Knockdown of WNT7B abolished the facilitation of osteogenic differentiation and the suppression of apoptosis induced by downregulation of miR-485-5p. DiscussionIn conclusion, MALAT1 promoted osteogenic differentiation and inhibited cell apoptosis through the miR-485-5p/WNT7B axis, which suggested that MALAT1 is a potential target to alleviate osteoporosis.

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