Bone marrow-derived mesenchymal stem cells (BMSCs) have the potential to differentiate into osteoblasts or adipocytes, and an imbalance between adipogenesis and osteogenesis causes age-related bone loss. In this study, we determined the influence of tumor necrosis factor receptor-associated factor 3 (TRAF3) on senescence and osteoblastic and adipocytic differentiation of rat BMSCs. TRAF3 expression increased during osteogenic differentiation but decreased during adipocytic differentiation of rat BMSCs, and compared with day 0 cultures, on day 14, the differences were significant. Overexpression of TRAF3 significantly promoted BMSC osteogenic differentiation and suppressed adipogenic differentiation and senescence. Furthermore, Traf3 was determined to be a target gene of miR-363-3p in BMSCs, and TRAF3 expression in BMSCs was reduced by miR-363-3p overexpression. This overexpression attenuated the effects of TRAF3 on BMSC adipogenic differentiation, osteogenic differentiation, and senescence. Taken together, these results uncovered the mechanism by which TRAF3 promotes BMSC osteogenic differentiation and suppresses adipogenic differentiation and senescence, indicating that the miR-363-3p–TRAF3 axis might be a novel therapeutic target for BMSC-based bone tissue engineering in osteoporosis.

中文翻译：

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TRAF3，MicroRNA-363-3p的目标，抑制衰老，并调节大鼠骨髓间充质干细胞成骨细胞和脂肪细胞分化之间的平衡。

骨髓间充质干细胞（BMSC）具有分化为成骨细胞或脂肪细胞的潜力，并且脂肪形成和成骨之间的不平衡会导致与年龄有关的骨质流失。在这项研究中，我们确定了肿瘤坏死因子受体相关因子3（TRAF3）对大鼠BMSCs的衰老以及成骨细胞和脂肪细胞分化的影响。在大鼠成骨细胞分化过程中，TRAF3表达增加，而在脂肪细胞分化过程中，TRAF3表达下降，并且与第0天培养相比，在第14天，差异显着。TRAF3的过表达显着促进BMSC成骨分化并抑制成脂分化和衰老。此外，Traf3确定miRNA-363-3p是BMSCs中miR-363-3p的靶基因，并且miR-363-3p过表达降低了TRAC3在BMSCs中的表达。这种过度表达减弱了TRAF3对BMSC成脂分化，成骨分化和衰老的作用。综上所述，这些结果揭示了TRAF3促进BMSC成骨分化并抑制成脂分化和衰老的机制，表明miR-363-3p–TRAF3轴可能是骨质疏松症中基于BMSC的骨组织工程的新型治疗靶标。