Beilun District People's Hospital of Ningbo, No. 1288, Lushan East Road, Ningbo, Zhejiang Province, 315800, China.
BMC Musculoskelet Disord. 2024 Nov 21;25(1):937. doi: 10.1186/s12891-024-08054-0.
To investigate the effects of zoledronic acid on muscle metabolism in mice with osteoporosis and sarcopenia and elucidate the possible underlying mechanism.
Twenty-four 8-week-old male C57BL/6J mice were randomly divided into four groups: non-suspension (N-SUS), suspension (SUS), suspension + zoledronic acid (ZA), and suspension + PTH(PTH) groups. Equal doses of saline, zoledronic acid, and PTH were administered subcutaneously. After 4 weeks, the mice were sacrificed, and body weight and muscle mass (gastrocnemius and soleus) were measured, the right tibia of mice was taken for micro-CT examination, and the muscle specimens were analyzed using HE staining, ATPase staining, western blotting, and real-time PCR.
Compared with the N-SUS group, the bone mineral density (BMD), trabecular bone relative volume (BV/TV) and trabecular bone number (Tb.N) were significantly decreased in the SUS group (P < 0.01), the trabecular bone separation(Tb.Sp)was significantly increased (P < 0.01), which was reversed in ZA and PTH group (P < 0.01).Compared to the SUS group, the body and muscle weights of the ZA and PTH groups were significantly increased. Compared to the SUS group, the muscle structure was less damaged, the proportion of type I muscle fibers was increased, and the protein expression of β-catenin and AKT were upregulated in the ZA and PTH groups(P < 0.05). In addition, the mRNA expression levels of Wnt3a, Wnt16, Myf5, and PI3K were significantly increased (P < 0.05), where as those of Myogenic Differentiation Antigen(MyoD )and Myogenin (MyoG) were significantly decreased (P < 0.05). No significant differences were observed between the ZA and PTH groups.
Zoledronic acid can reduce muscle loss and damage by upregulating the mRNA expression of Wnt and PI3K and the protein expression of β-catenin and AKT.Our results provide a novel basis for the development of drugs for the treatment of osteoporosis combined with sarcopenia.
探讨唑来膦酸对骨质疏松伴肌肉减少症小鼠肌肉代谢的影响，并阐明其可能的作用机制。
将 24 只 8 周龄雄性 C57BL/6J 小鼠随机分为 4 组：非悬吊（N-SUS）组、悬吊（SUS）组、悬吊+唑来膦酸（ZA）组和悬吊+甲状旁腺素（PTH）组。皮下注射等剂量生理盐水、唑来膦酸和 PTH。4 周后处死小鼠，测量体重和肌肉质量（比目鱼肌和跖肌），取右侧胫骨进行 micro-CT 检查，肌肉标本进行 HE 染色、ATP 酶染色、Western blot 和实时 PCR 分析。
与 N-SUS 组相比，SUS 组的骨密度（BMD）、骨小梁相对体积（BV/TV）和骨小梁数量（Tb.N）明显降低（P<0.01），骨小梁间距（Tb.Sp）明显增加（P<0.01），而 ZA 和 PTH 组则相反（P<0.01）。与 SUS 组相比，ZA 和 PTH 组的体质量和肌肉质量明显增加。与 SUS 组相比，ZA 和 PTH 组的肌肉结构损伤较小，Ⅰ型肌纤维比例增加，β-catenin 和 AKT 蛋白表达上调（P<0.05）。此外，Wnt3a、Wnt16、Myf5 和 PI3K 的 mRNA 表达水平显著升高（P<0.05），而 Myogenic Differentiation Antigen（MyoD）和 Myogenin（MyoG）的 mRNA 表达水平显著降低（P<0.05）。ZA 和 PTH 组之间无显著差异。
唑来膦酸通过上调 Wnt 和 PI3K 的 mRNA 表达以及β-catenin 和 AKT 的蛋白表达，减少肌肉丢失和损伤。我们的研究结果为开发治疗骨质疏松合并肌肉减少症的药物提供了新的依据。
