Department of Orthopedics, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing, China.
Department of Orthopedics, Air Force Hospital of Eastern Theater, Anhui Medical University, Nanjing, China.
Aging Cell. 2021 Feb;20(2):e13298. doi: 10.1111/acel.13298. Epub 2021 Jan 13.
Impaired osteoblast function is involved in osteoporosis, and microRNA (miRNA) dysregulation may cause abnormal osteoblast osteogenic activity. However, the influence of miRNA on osteoblast activity and the underlying mechanisms remain elusive. In this study, miR-103-3p was found to be negatively correlated with bone formation in bone specimens from elderly women with fractures and ovariectomized (OVX) mice. Additionally, miR-103-3p directly targeted Mettl14 to inhibit osteoblast activity, and METTL14-dependent N -methyladenosine (m A) methylation inhibited miR-103-3p processing by the microprocessor protein DGCR8 and promoted osteoblast activity. Moreover, miR-103-3p inhibited bone formation in vivo, and therapeutic inhibition of miR-103-3p counteracted the decreased bone formation in OVX mice. Further, METTL14 was negatively correlated with miR-103-3p but positively correlated with bone formation in bone specimens from elderly women with fractures and OVX mice. Collectively, our results highlight the critical roles of the miR-103-3p/METTL14/m A signaling axis in osteoblast activity, identifying this axis as a potential target for ameliorating osteoporosis.
成骨细胞功能受损与骨质疏松症有关，miRNA（microRNA）失调可能导致成骨细胞成骨活性异常。然而，miRNA 对成骨细胞活性的影响及其潜在机制仍不清楚。在这项研究中，发现在骨折老年女性和去卵巢（OVX）小鼠的骨标本中，miR-103-3p 与骨形成呈负相关。此外，miR-103-3p 直接靶向 Mettl14 抑制成骨细胞活性，而 METTL14 依赖性 N6-甲基腺苷（m A）甲基化抑制微处理器蛋白 DGCR8 对 miR-103-3p 的加工，并促进成骨细胞活性。此外，miR-103-3p 抑制体内骨形成，而抑制 miR-103-3p 的治疗性抑制可逆转 OVX 小鼠骨形成减少。此外，METTL14 与 miR-103-3p 呈负相关，但与骨折老年女性和 OVX 小鼠的骨标本中的骨形成呈正相关。总之，我们的研究结果强调了 miR-103-3p/METTL14/m A 信号轴在成骨细胞活性中的关键作用，确定该信号轴为改善骨质疏松症的潜在靶点。
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