Rantanen J, Hurme T, Lukka R, Heino J, Kalimo H
Department of Pathology, Paavo Nurmi Center, University of Turku, Finland.
Lab Invest. 1995 Mar;72(3):341-7.
Regeneration of mature skeletal muscle recapitulates closely fetal myogenesis. It is initiated by activation of the reserve myogenic precursor cells, the satellite cells, which proliferate, differentiate into myoblasts expressing muscle-specific proteins, fuse into myotubes, and finally mature into myofibers. The MyoD family of transcription factors participates in the regulation of the complex phenomenon of myogenic differentiation during development and in vitro. The function of these transcription factors in the regeneration of injured mature skeletal muscle in vivo is, however, still unclear.
To clarify the primary events in myogenic precursor cell activation, the expression of myogenin was examined in rats 1 to 48 hours after either a contusion injury to the gastrocnemius or after toxic injury to the soleus muscle. Myogenin mRNA expression was studied by Northern blot hybridizations, and the results were correlated with the onsets of the mitotic activity (i.e., incorporation of bromodeoxyuridine) of the satellite cells and of the production of the myogenin and MyoD1 proteins, as well as muscle-specific intermediate filament protein, desmin.
Both forms of muscle injury produced myofiber necrosis, followed by the activation of the satellite cells. The first sign of myogenic differentiation, an increase in myogenin mRNA expression, occurred between 4 and 8 hours after injury. The first desmin-, MyoD1- and myogenin-positive myoblasts were seen after 12 hours, but satellite cell proliferation was not seen until 24 hours after the injury.
The schedule of the events in our study contradicts the general concept that differentiation should follow proliferation. To explain this discrepancy, we propose that there are two populations of precursor cells: committed satellite cells, which are ready for immediate differentiation without preceding cell division, and stem satellite cells, which undergo mitosis before providing one daughter cell for differentiation and another for future proliferation.
成熟骨骼肌的再生与胎儿期肌发生过程极为相似。它由储备肌源性前体细胞即卫星细胞的激活引发，卫星细胞增殖，分化为表达肌肉特异性蛋白的成肌细胞，融合形成肌管，最终成熟为肌纤维。MyoD转录因子家族参与发育过程中和体外肌源性分化这一复杂现象的调控。然而，这些转录因子在体内受损成熟骨骼肌再生中的功能仍不清楚。
为阐明肌源性前体细胞激活的初始事件，在大鼠腓肠肌受到钝挫伤或比目鱼肌受到毒性损伤后1至48小时，检测了肌细胞生成素的表达。通过Northern印迹杂交研究肌细胞生成素mRNA表达，并将结果与卫星细胞的有丝分裂活性（即溴脱氧尿苷掺入）起始、肌细胞生成素和MyoD1蛋白以及肌肉特异性中间丝蛋白结蛋白的产生相关联。
两种形式的肌肉损伤均导致肌纤维坏死，随后卫星细胞被激活。肌源性分化的首个迹象，即肌细胞生成素mRNA表达增加，发生在损伤后4至8小时。在12小时后可见首个结蛋白、MyoD1和肌细胞生成素阳性的成肌细胞，但直到损伤后24小时才观察到卫星细胞增殖。
我们研究中事件的时间安排与分化应在增殖之后这一普遍概念相矛盾。为解释这一差异，我们提出存在两种前体细胞群体：定向卫星细胞，它们无需先进行细胞分裂即可立即分化；以及干细胞卫星细胞，它们在为分化提供一个子代细胞并为未来增殖提供另一个子代细胞之前会进行有丝分裂。
