The muscle satellite cell is established as the major stem cell contributing to fiber growth and repair. p38 MAPK signaling is essential for myoblast differentiation and in particular for up-regulation of promyogenic Igf2 expression. p38 exists as four isoforms (alpha, beta, gamma, and delta), of which p38gamma is uniquely abundant in muscle.
View Article and Find Full Text PDFDuring the differentiation of muscle satellite cells, committed myoblasts respond to specific signalling cues by exiting the cell cycle, migrating, aligning, expressing muscle-specific genes and finally fusing to form multinucleated myotubes. The predominant foetal growth factor, IGF-2, initiates important signals in myogenesis. The aim of this study was to investigate whether ERK5 and its upstream MKK activator, MEK5, were important in the pro-myogenic actions of IGF-2.
View Article and Find Full Text PDFObjectives: Socioeconomic factors are associated with reduced health status in low-income populations. We sought to identify affordable employment benefit packages that might ameliorate these socioeconomic factors and would be consonant with employees' priorities.
Methods: Working in groups (n = 53), low-income employees (n = 408; 62% women, 65% Black) from the Washington, DC, and Baltimore, Md, metropolitan area, participated in a computerized exercise in which they expressed their preference for employment benefit packages intended to address socioeconomic determinants of health.
Cell-cell contact is essential for appropriate co-ordination of development and it initiates significant signalling events. During myogenesis, committed myoblasts migrate to sites of muscle formation, align and form adhesive contacts that instigate cell-cycle exit and terminal differentiation into multinucleated myotubes; thus myogenesis is an excellent paradigm for the investigation of signals derived from cell-cell contact. PI3-K and p38 MAPK are both essential for successful myogenesis.
View Article and Find Full Text PDFIGF-binding protein-5 (IGFBP-5) is abundant in serum and bone during normal skeletal development, but levels decrease in osteoporosis. Studies have shown that IGFBP-5 stimulates markers of bone formation by potentiating IGF actions and by IGF-independent actions. To test the hypothesis that IGFBP-5 promotes the acquisition of bone mineral density (BMD), we generated transgenic (Tg) mice overexpressing Igfbp5 using a cytomegalovirus enhancer and beta-actin promoter (CMV/betaA).
View Article and Find Full Text PDFActivation of either the phosphatidylinositol 3-kinase (PI 3-kinase)/Akt or the p38 mitogen-activated protein kinase (MAPK) signaling pathways accelerates myogenesis but only when the reciprocal pathway is functional. We therefore examined the hypothesis that cross-activation between these signaling cascades occurs to orchestrate myogenesis. We reveal a novel and reciprocal cross-talk and activation between the PI 3-kinase/Akt and p38 MAPK pathways that is essential for efficient myoblast differentiation.
View Article and Find Full Text PDFIgfbp5 is upregulated during the differentiation of several key cell lineages and in some tumours; the function of IGFBP-5 in these physiological and pathological situations is unknown. Since IGFBP-5 contains sequence motifs consistent with IGF-independent actions, the aim of these studies was to distinguish between IGF-dependent and -independent actions of IGFBP-5. Myc-tagged wild-type (termed wtIGFBP-5) and non-IGF binding mouse Igfbp5 (termed mutIGFBP-5) cDNAs were generated and used to transfect C2 myoblasts, a cell line that undergoes differentiation to myotubes in an IGF- and IGFBP-5-regulated manner.
View Article and Find Full Text PDFAntibodies to alpha-elastin peptides, amyloid P component, lysozyme and plasma protease inhibitors have been used in an immunoperoxidase method to stain elastic fibres in frozen sections of human breast tissues. A loss of immunoreactivity seen in formalin-fixed, paraffin-embedded sections was reversed by a preliminary proteolysis. Differences in the tinctorial dye and immunohistochemical staining patterns following proteolysis by a variety of enzymes suggests a selective unmasking or removal of elastic fibre components and thus the presence of separate binding sites for individual antibodies and tinctorial dyes.
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