Qianggu Decoction Alleviated Osteoporosis by Promoting Osteogenesis of BMSCs through Mettl3-Mediated m⁶A Methylation.

IF 4.3 3区材料科学 Q1 ENGINEERING, ELECTRICAL & ELECTRONIC ACS Applied Electronic Materials Pub Date : 2024-07-25 DOI:10.1002/adbi.202400341

Yuchen Wang, Weizhong Yu, Yuan E, Lining Rui, Chuan Jia, Wenke Zhu

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Abstract

Osteoporosis development is linked to abnormal bone marrow mesenchymal stem cells (BMSCs) differentiation. N6-methyladenosine (m⁶A), a prevalent mRNA modification, is known to influence BMSCs' osteogenic capacity. Qianggu decoction (QGD), a traditional Chinese medicine for osteoporosis, has unknown effects on BMSCs differentiation. This study investigates QGD's impact on BMSCs and its potential to ameliorate osteoporosis through m⁶A regulation. Using Sprague-Dawley (SD) rats with ovariectomy-induced osteoporosis, it is evaluated QGD's antiosteoporotic effects through micro-CT, histology, Western blotting, and osteoblastogenesis markers. QGD is found to enhance bone tissue growth and upregulate osteogenic markers Runx2, OPN, and OCN. It also promoted BMSCs osteogenic differentiation, as shown by increased calcium nodules and ALP activity. QGD treatment significantly increased m⁶A RNA levels and Mettl3 expression in BMSCs. Silencing Mettl3 with siRNA negated QGD's osteogenic effects. Collectively, QGD may improve BMSCs differentiation and mitigate osteoporosis, potentially through Mettl3-mediated m⁶A modification.

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羌活煎剂通过Mettl3介导的m6A甲基化促进BMSCs骨生成，从而缓解骨质疏松症

骨质疏松症的发生与骨髓间充质干细胞（BMSCs）分化异常有关。N6-甲基腺苷（m6A）是一种常见的 mRNA 修饰，已知会影响骨髓间充质干细胞的成骨能力。羌活汤（QGD）是一种治疗骨质疏松症的传统中药，其对 BMSCs 分化的影响尚不清楚。本研究探讨了羌活汤对 BMSCs 的影响及其通过 m6A 调节改善骨质疏松症的潜力。本研究使用卵巢切除术诱发骨质疏松症的斯普拉格-道利（SD）大鼠，通过显微 CT、组织学、Western 印迹和成骨细胞生成标记物评估 QGD 的抗骨质疏松症作用。研究发现，QGD 能促进骨组织生长，并上调成骨标志物 Runx2、OPN 和 OCN。它还能促进 BMSCs 成骨分化，表现为钙结节和 ALP 活性的增加。QGD 处理可明显提高 m6A RNA 水平和 BMSCs 中 Mettl3 的表达。用 siRNA 沉默 Mettl3 则会抵消 QGD 的成骨作用。总之，QGD可能通过Mettl3介导的m6A修饰改善BMSCs分化并缓解骨质疏松症。

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