Osteoporosis (OP) is one of the most common chronic metabolic bone diseases in the seniors and postmenopausal women. Plenty of microRNAs (miRNAs) have been confirmed to be involved in OP progression. However, the role of miR-655-3p in osteogenic differentiation and bone formation was still unclear. In this study, we aimed to investigate the cellular function of miR-655-3p and its underlying mechanism in OP. We found that miR-655-3p expression was downregulated in both ovariectomized (OVX) mice bone tissues and MC3T3-E1 cells treated with simulated microgravity (MG). MiR-655-3p overexpression facilitated cell differentiation but suppressed cell apoptosis of MC3T3-E1 cells induced by simulated MG. Mechanistically, we confirmed that lysine-specific histone demethylase 1 (LSD1) is a downstream target gene of miR-655-3p. Furthermore, overexpression of miR-655-3p activated the bone morphogenetic protein 2 (BMP-2)/decapentaplegic homolog (Smad) signaling pathway by suppressing LSD1 expression. Moreover, LSD1 knockdown accelerated osteogenic differentiation and inhibited apoptosis in MC3T3-E1 cells under simulated MG. Additionally, the OVX mouse model was established to investigate the role of miR-655-3p/LSD1 axis in vivo. The results demonstrated that LSD1 could reverse the effects triggered by the injection of adeno-associated virus-miR-655-3p on OP development. Further investigations revealed that miR-655-3p boosted osteogenic differentiation through LSD1/BMP-2/Smad signaling pathway. In summary, these findings implied a potential value of miR-655-3p in OP therapy.

中文翻译：

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MiR-655-3p通过靶向LSD1和激活BMP-2 / Smad信号通路来抑制骨质疏松的进展。

骨质疏松症（OP）是老年人和绝经后妇女中最常见的慢性代谢性骨病之一。大量的microRNA（miRNA）已被证实参与OP进展。但是，miR-655-3p在成骨分化和骨形成中的作用仍不清楚。在这项研究中，我们旨在研究miR-655-3p的细胞功能及其在OP中的潜在机制。我们发现在卵巢切除的（OVX）小鼠骨骼组织和用模拟微重力（MG）处理的MC3T3-E1细胞中，miR-655-3p表达均下调。MiR-655-3p过表达促进细胞分化，但抑制了模拟MG诱导的MC3T3-E1细胞的细胞凋亡。从机制上讲，我们确认赖氨酸特异性组蛋白脱甲基酶1（LSD1）是miR-655-3p的下游靶基因。此外，miR-655-3p的过表达通过抑制LSD1的表达激活了骨形态发生蛋白2（BMP-2）/去功能化同系物（Smad）信号通路。此外，LSD1敲低加速成骨分化并抑制模拟MG下MC3T3-E1细胞的凋亡。此外，建立OVX小鼠模型以研究miR-655-3p / LSD1轴在体内的作用。结果表明，LSD1可以逆转注射腺相关病毒miR-655-3p触发的对OP发育的影响。进一步的研究表明，miR-655-3p通过LSD1 / BMP-2 / Smad信号通路促进了成骨分化。总之，这些发现暗示了miR-655-3p在OP治疗中的潜在价值。