Irisin Correlates Positively With BMD in a Cohort of Older Adult Patients and Downregulates the Senescent Marker p21 in Osteoblasts
Irisin Correlates Positively With BMD in a Cohort of Older Adult Patients and Downregulates the Senescent Marker p21 in Osteoblasts
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DOI：
10.1002/jbmr.4192
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发表时间：
2020-10-29
影响因子：
6.2
通讯作者：
Grano, Maria
中科院分区：
文献类型：
--
作者：
Colaianni, Graziana;Errede, Mariella;Grano, Maria
Irisin是一种在小鼠和人类运动期间由骨骼肌产生的肌因子。我们先前表明，鸢尾素治疗改善不动诱导的骨质疏松症和肌肉萎缩的小鼠。人体数据显示，在运动员和健康儿童人群中，鸢尾素与骨矿物质密度（BMD）呈正相关。然而，这种肌因子在同一人群中对肌肉和骨骼状态的作用仍有待确定。为此，招募了62例接受全髋关节或膝关节置换术的患者（年龄68.71 ± 12.31岁）。我们的研究结果显示，血清中鸢尾素水平与年龄呈负相关（R = -0.515; p = .000018），与股骨BMD（R = 0.619; p = .001）和椎骨BMD（R = 0.201; p = .0001）呈正相关。在肌肉活检中，鸢尾素与Fndc 5 mRNA呈正相关（R = 0.248; p = 0.016），在骨活检中，鸢尾素与骨钙素（Ocn）mRNA呈正相关（R = 0.708; p = 0.006）。在骨骼肌中，FNDC 5阳性纤维与全股骨BMD呈正相关（R = 0.765; p = .0014）和股骨颈BMD（R = 0.575;有趣的是，通过分析患者除以他们的T评分，我们发现与年龄和性别匹配的健康对照相比，骨质减少/骨质疏松（OP）患者中的鸢尾素水平较低（p = 0.0011）。通过分析衰老标志物p21，我们发现与对照组相比，OP患者的骨活检组织中其mRNA表达显著增加。因此，我们在体外研究是否rec-irisin对这种衰老标志物有直接影响，表明p21 mRNA的表达显着下调成骨细胞的治疗与irisin。总体而言，这些结果表明，较高的鸢尾素水平与年龄相关的骨质疏松症的发生率较低，并且鸢尾素可以有效地延缓成骨细胞的衰老过程，这表明这种肌因子具有潜在的衰老作用。(c)2020年美国骨骼与矿物研究学会（ASBMR）。
Irisin is a myokine produced by skeletal muscle during exercise in both mice and humans. We previously showed that irisin treatment ameliorates immobility-induced osteoporosis and muscular atrophy in mice. Data in humans showed a positive association between irisin and bone mineral density (BMD) in athletes and a population of healthy children. However, the role of this myokine regarding the state of muscle and bone in the same population remained to be determined. For this purpose, 62 patients (age 68.71 +/- 12.31 years) undergoing total hip or knee replacement were recruited. Our results showed that irisin serum levels negatively correlated with age (R = -0.515; p = .000018) and positively correlated with femoral BMD (R = 0.619; p = .001) and vertebral BMD (R = 0.201; p = .0001). Irisin was also positively associated with Fndc5 mRNA in muscle biopsies (R = 0.248; p = .016), as well as with Osteocalcin (Ocn) mRNA in bone biopsies (R = 0.708; p = .006). In skeletal muscle, FNDC5 positive fibers positively correlate with BMD of total femur (R = 0.765; p = .0014) and BMD of femoral neck (R = 0.575; p = .031), Interestingly, by analyzing patients divided by their T-score, we found lower irisin levels (p = .0011) in patients with osteopenia/osteoporosis (OP) compared to healthy controls matched for age and sex. By analyzing the senescence marker p21, we found a significant increase of its mRNA expression in the bone biopsies of OP patients compared to control ones. Therefore, we investigated in vitro whether rec-irisin had a direct effect on this senescence marker, showing that p21 mRNA expression was significantly downregulated in osteoblasts by the treatment with irisin. Overall, these results indicate that higher irisin levels are associated with a lower rate of age-related osteoporosis and that irisin could be effective in delaying the osteoblast aging process, suggesting a potential senolytic action of this myokine. (c) 2020 American Society for Bone and Mineral Research (ASBMR).