Falvino Angela, Bonanni Roberto, Gasperini Beatrice, Cariati Ida, Chiavoghilefu Angela, Smakaj Amarildo, Visconti Virginia Veronica, Botta Annalisa, Iundusi Riccardo, Gasbarra Elena, Tancredi Virginia, Tarantino Umberto
Department of Biomedicine and Prevention, "Tor Vergata" University of Rome, 00133 Rome, Italy.
Department of Applied Clinical and Biotechnological Sciences, University of L'Aquila, 67100 L'Aquila, Italy.
Biomedicines. 2025 May 31;13(6):1350. doi: 10.3390/biomedicines13061350.
: Cellular aging represents a crucial element in the progression of musculoskeletal diseases, contributing to muscle atrophy, functional decline, and alterations in bone turnover, which promote fragility fractures. However, knowledge about expression patterns of factors potentially involved in aging and senescence at the tissue level remains limited. Our pilot study aimed to characterize the expression profile of cell cycle regulators, factors released by aged cells, and sirtuin 1 (SIRT1) in the muscle tissue of 26 elderly patients undergoing hip arthroplasty, including 13 with low-energy fracture and 13 with osteoarthritis (OA). : The mRNA expression levels of cyclin-dependent kinase inhibitor 1A (), cyclin-dependent kinase inhibitor 1B (), cyclin-dependent kinase inhibitor 2A (), , tumor necrosis factor alpha (), interleukin-1 beta ), interleukin-6 (), interleukin-15 (), chemokine (C-C motif) ligand 2 (), chemokine (C-C motif) ligand 3 (), growth differentiation factor 15 (), and were evaluated in muscle tissue by qRT-PCR. In addition, immunohistochemistry and Western blotting analysis were conducted to measure the protein levels of SIRT1. : A marked muscle atrophy was observed in fractured patients compared to the OA group, in association with an up-regulation of cell cycle regulators and factors released by the aged cells. The expression of matrix metallopeptidase 3 (), plasminogen activator inhibitor 1 (), and fas cell surface death receptor () was also investigated, although no significant differences were observed between the two experimental groups. Notably, SIRT1 expression was significantly higher in OA patients, confirming its role in maintaining muscle health during aging. : Further studies will be needed to clarify the role of SIRT1 in the senescence characteristic of age-related musculoskeletal disorders, counteracting the muscle atrophy that predisposes to fragility fractures.
细胞衰老在肌肉骨骼疾病的进展中是一个关键因素,会导致肌肉萎缩、功能衰退以及骨转换改变,进而促使脆性骨折的发生。然而,关于潜在参与衰老和组织水平衰老过程的因子表达模式的了解仍然有限。我们的初步研究旨在描述26例接受髋关节置换术的老年患者肌肉组织中细胞周期调节因子、衰老细胞释放的因子以及沉默调节蛋白1(SIRT1)的表达谱,其中包括13例低能量骨折患者和13例骨关节炎(OA)患者。通过qRT-PCR评估肌肉组织中细胞周期蛋白依赖性激酶抑制剂1A()、细胞周期蛋白依赖性激酶抑制剂1B()、细胞周期蛋白依赖性激酶抑制剂2A()、、肿瘤坏死因子α()、白细胞介素-1β()、白细胞介素-6()、白细胞介素-15()、趋化因子(C-C基序)配体2()、趋化因子(C-C基序)配体3()、生长分化因子15()和的mRNA表达水平。此外,进行免疫组织化学和蛋白质印迹分析以检测SIRT1的蛋白水平。与OA组相比,骨折患者出现明显的肌肉萎缩,同时伴有细胞周期调节因子和衰老细胞释放因子的上调。还研究了基质金属肽酶3()、纤溶酶原激活物抑制剂1()和Fas细胞表面死亡受体()的表达,尽管两个实验组之间未观察到显著差异。值得注意的是,OA患者中SIRT1的表达显著更高,证实了其在衰老过程中维持肌肉健康的作用。需要进一步研究来阐明SIRT1在与年龄相关的肌肉骨骼疾病衰老特征中的作用,以对抗易导致脆性骨折的肌肉萎缩。
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