Ageing Bone Research Program, Sydney Medical School Nepean, The University of Sydney, Penrith, NSW 2750, Australia.
Mech Ageing Dev. 2011 Nov-Dec;132(11-12):552-9. doi: 10.1016/j.mad.2011.09.004. Epub 2011 Oct 1.
Sarcopenia and osteopenia are two common components of the frailty syndrome that may share a common underlying mechanism. Since frailty has been associated with increased fat infiltration in muscle and bone, we hypothesized that lamin A/C, a protein of the nuclear envelope that regulates adipose differentiation, could be associated with the pathophysiology of both osteo and sarcopenia in the frailty syndrome. Four-week-old lamin A/C null (Lmna(-/-)), heterozygous (Lmna(+/-)) and wild type (WT) mice were sacrificed and their mid-thigh analyzed for fat infiltration using invasive (histology) and non-invasive (μCT) methods. Lmna(-/-) mice showed a significant increase in inter- (4-fold) and intra-myofiber (2.5-fold) fat and marrow fat infiltration (~40-fold), with a significant decrease in muscle volume (-42.8%) and bone volume (-21.8%), as compared with WT controls. Furthermore, fat infiltration happened concomitantly with a significant decline in muscle and bone strength in Lmna(-/-) mice. From a mechanistic approach, high levels of pro-adipogenic factors PPARγ and C/EBPα were associated with a reduction in myogenic and osteogenic factors from the Wnt-10b/β-catenin signalling pathway in Lmna(-/-) mice. In conclusion, lamin A/C could constitute the determinant factor in the pathogenesis and potential treatment of both sarcopenia and osteopenia, which are commonly observed in the frailty syndrome.
肌肉减少症和骨质疏松症是衰弱综合征的两个常见组成部分，它们可能具有共同的潜在机制。由于衰弱与肌肉和骨骼中脂肪浸润的增加有关，我们假设核膜中的一种蛋白质 lamin A/C，它调节脂肪分化，可以与衰弱综合征中骨和肌肉减少症的病理生理学相关。4 周龄 lamin A/C 敲除（Lmna(-/-)）、杂合子（Lmna(+/-)）和野生型（WT）小鼠被处死，其大腿中段用侵袭性（组织学）和非侵袭性（μCT）方法分析脂肪浸润。与 WT 对照相比，Lmna(-/-) 小鼠的肌间（4 倍）和肌内（2.5 倍）脂肪以及骨髓脂肪浸润（40 倍）显著增加，肌肉体积减少（42.8%），骨体积减少（~21.8%）。此外，脂肪浸润与 Lmna(-/-) 小鼠肌肉和骨骼强度的显著下降同时发生。从机制上看，高水平的前脂肪生成因子 PPARγ 和 C/EBPα与 Lmna(-/-) 小鼠中 Wnt-10b/β-catenin 信号通路的成肌和成骨因子减少有关。总之，lamin A/C 可能是衰弱综合征中常见的肌肉减少症和骨质疏松症发病机制和潜在治疗的决定因素。
