Synergic stimulation of laminin and epidermal growth factor facilitates the myoblast growth through promoting migration.
ABSTRACT The dynamic behaviors of human skeletal muscle myoblasts were investigated in the culture on a laminin-coated surface in the presence of 100 ng/ml epidermal growth factor (EGF) in medium. The coexistence of laminin and EGF caused the enhancement of myoblast migration, giving an average migration rate of 62.0 microm/h, which was 2.7 times that on a plain surface. This encouraged migration could be a driving force to separate the dividing cells from each other, accompanied by shortened disjunction time of daughter cells to complete cytokinesis. In addition, the synergic effect of laminin and EGF led to the promotion of myoblast growth with keeping a relatively high fraction of proliferative cells during the culture for 150 h, which is considered to arise from the reduced frequency of cell-cell contacts during cytokinesis and thereby suppressing the process towards myotube formation after cell division.
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ABSTRACT: Recent advances are revealing quantitative aspects of cytokinesis. Further, genetic analyses and cell imaging are providing insights into the molecular dynamics of cleavage furrow ingression as well as further refining our knowledge of the zones of the mitotic spindle that regulate the contractile properties of the overlying cortex. Ultimately, however, cortical mechanics are the result of signals that emanate from the mitotic spindle. A genuine quantitative understanding of cytokinesis must include a thorough analysis of the mechanical properties of the cortex and how signals modify these properties to dictate a well-controlled, error-free cytokinesis.Current Opinion in Cell Biology 05/2004; 16(2):182-8. · 11.41 Impact Factor
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ABSTRACT: Differentiation of skeletal myoblasts into multinucleated myotubes is a multistep process orchestrated by several families of transcription factors, including myogenic bHLH and NFAT proteins. The activities of these factors and formation of myotubes are regulated by signal transduction pathways, but few extracellular factors that might initiate such signals have been identified. One exception is a cell surface complex containing promyogenic Ig superfamily members (CDO and BOC) and cadherins. Netrins and their receptors are established regulators of axon guidance, but little is known of their function outside the nervous system. We report here that myoblasts express the secreted factor netrin-3 and its receptor, neogenin. These proteins stimulate myotube formation and enhance myogenic bHLH- and NFAT-dependent transcription. Furthermore, neogenin binds to CDO in a cis fashion, and myoblasts lacking CDO are defective in responding to recombinant netrin. It is proposed that netrin-3 and neogenin may promote myogenic differentiation by an autocrine mechanism as components of a higher order complex of several promyogenic cell surface proteins.The Journal of Cell Biology 12/2004; 167(3):493-504. · 10.82 Impact Factor
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ABSTRACT: We have assessed the ability of skeletal myoblasts to form long-term, differentiated grafts in ventricular myocardium. C2C12 myoblasts were grafted directly into the heart of syngeneic mice. Viable grafts were observed as long as 3 mo after implantation. Immunohistological analyses revealed the presence of differentiated myotubes that stably expressed the skeletal myosin heavy chain isoform. Thymidine uptake studies indicated that virtually all of the grafted skeletal myocytes were withdrawn from the cell cycle by 14 d after grafting. Graft myocytes exhibited ultrastructural characteristics typical of differentiated myotubes. Graft formation and the associated myocardial remodeling did not induce overt cardiac arrhythmia. This study indicates that the myocardium can serve as a stable platform for skeletal myoblast grafts. The long-term survival, differentiated phenotype, and absence of sustained proliferative activity observed in myoblast grafts raise the possibility that similar grafting approaches may be used to replace diseased myocardium. Furthermore, the genetic tractability of myoblasts could provide a useful means for the local delivery of recombinant molecules to the heart.Journal of Clinical Investigation 10/1993; 92(3):1548-54. · 12.81 Impact Factor