二甲双胍通过阻断 HMGB1 的易位，抑制衰老小鼠的肌腱炎症和衰老，从而改善肌腱退化。
Metformin improves tendon degeneration by blocking translocation of HMGB1 and suppressing tendon inflammation and senescence in aging mice.
机构信息
MechanoBiology Laboratory, Department of Orthopaedic Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Department of Bioengineering, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
出版信息
J Orthop Res. 2023 Jun;41(6):1162-1176. doi: 10.1002/jor.25470. Epub 2022 Nov 7.
This study aimed to characterize aging-induced tendinopathy in mouse Achilles tendon and also to assess the treatment effects of metformin (Met) on aging tendon. We showed that compared to young tendon, aging tendon was in an inflammatory and senescent state as shown by increased expression of inflammatory disulfide HMGB1 (dsHMGB1), inflammatory macrophage marker CD68, and senescent cell markers SA-β-gal, p53, and p16. Moreover, aging tendon was degenerated marked by accumulation of proteoglycans and lipids in its interior. However, treatment of aging tendon by intraperitoneal (IP) injection of Met, a specific inhibitor of HMGB1, reduced dsHMGB1 levels, decreased the expression of CD68, SA-β-gal, CCN1, and p16 in vitro and in vivo. Furthermore, Met treatment also increased the number of NS, SSEA-1, and CD73 positive stem cells in culture and improved the tendon structure in aging mouse. These findings of this study indicate that Met exerts anti-inflammatory and anti-senescent effects on aging tendon.
本研究旨在描述小鼠跟腱老化相关的腱病，并评估二甲双胍（Met）对老化腱的治疗效果。我们发现与年轻腱相比，老化腱处于炎症和衰老状态，表现为炎症二硫键高迁移率族蛋白 1（dsHMGB1）、炎症巨噬细胞标志物 CD68 和衰老细胞标志物 SA-β-gal、p53 和 p16 的表达增加。此外，老化腱发生退行性变，其内部堆积了大量的蛋白聚糖和脂质。然而，通过腹腔（IP）注射 Met（一种 HMGB1 的特异性抑制剂）对老化腱进行治疗，可降低 dsHMGB1 水平，减少体外和体内 CD68、SA-β-gal、CCN1 和 p16 的表达。此外，Met 治疗还增加了培养中 NS、SSEA-1 和 CD73 阳性干细胞的数量，并改善了衰老小鼠的腱结构。本研究的这些发现表明，Met 对老化腱具有抗炎和抗衰老作用。
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