Department of Pathology, University of Gothenburg, Sahlgrenska University Hospital, Gothenburg, SE, 413 45, Sweden.
BMC Musculoskelet Disord. 2012 Dec 29;13:262. doi: 10.1186/1471-2474-13-262.
The formation of contractile myofibrils requires the stepwise onset of expression of muscle specific proteins. It is likely that elucidation of the expression patterns of muscle-specific sarcomeric proteins is important to understand muscle disorders originating from defects in contractile sarcomeric proteins.
We investigated the expression profile of a panel of sarcomeric components with a focus on proteins associated with a group of congenital disorders. The analyses were performed in cultured human skeletal muscle cells during myoblast proliferation and myotube development.
Our culture technique resulted in the development of striated myotubes and the expression of adult isoforms of the sarcomeric proteins, such as fast TnI, fast TnT, adult fast and slow MyHC isoforms and predominantly skeletal muscle rather than cardiac actin. Many proteins involved in muscle diseases, such as beta tropomyosin, slow TnI, slow MyBPC and cardiac TnI were readily detected in the initial stages of muscle cell differentiation, suggesting the possibility of an early role for these proteins as constituent of the developing contractile apparatus during myofibrillogenesis. This suggests that in disease conditions the mechanisms of pathogenesis for each of the mutated sarcomeric proteins might be reflected by altered expression patterns, and disturbed assembly of cytoskeletal, myofibrillar structures and muscle development.
In conclusion, we here confirm that cell cultures of human skeletal muscle are an appropriate tool to study developmental stages of myofibrillogenesis. The expression of several disease-associated proteins indicates that they might be a useful model system for studying the pathogenesis of muscle diseases caused by defects in specific sarcomeric constituents.
收缩性肌纤维的形成需要肌肉特异性蛋白表达的逐步启动。阐明肌肉特异性肌节蛋白的表达模式对于理解源自收缩性肌节蛋白缺陷的肌肉疾病可能很重要。
我们研究了一组肌节成分的表达谱，重点是与一组先天性疾病相关的蛋白。这些分析是在培养的人类骨骼肌细胞中进行的，涉及成肌细胞增殖和肌管发育过程。
我们的培养技术导致了有条纹的肌管的发育和肌节蛋白的成人同工型的表达，例如快肌 TnI、快肌 TnT、成人快肌和慢肌 MyHC 同工型，以及主要是骨骼肌而不是心肌肌动蛋白。许多涉及肌肉疾病的蛋白，如β原肌球蛋白、慢肌 TnI、慢肌 BPC 和心肌 TnI，在肌肉细胞分化的早期阶段很容易被检测到，这表明这些蛋白作为肌原纤维发生过程中发育收缩装置的组成部分，可能在早期发挥作用。这表明，在疾病情况下，每种突变肌节蛋白的发病机制可能反映在改变的表达模式中，以及细胞骨架、肌节结构和肌肉发育的失调组装中。
总之，我们在这里证实了人类骨骼肌细胞培养是研究肌原纤维发生发育阶段的合适工具。几种疾病相关蛋白的表达表明，它们可能是研究特定肌节成分缺陷引起的肌肉疾病发病机制的有用模型系统。
