The role of cells expressing connective tissue growth factor CTGF and ErbB4 receptor during regeneration and/or skeletomuscular development

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It was reported that the gene expression of ErbB4 receptor was up regulated by addition of connective tissue growth factor(CTGF) under the cultivation of a chondrocytic cell line HCS2/8. This suggests, that ErbB4 receptor may have certain relationship to CTGF in chondrogenesis. Therefore, in situ hybridization was performed with riboprobes to analyze the gene expression pattern of ErbB4 and CTGF during mouse development. The gene expressions of ErbB4 were detected some tissues through all developmental stages, like in somites, sensory ganglia, peripheral nerves, cardiac muscles, lungs and chondrocytes in skeletal formation etc. However, a dual phase gene expression patterns like that of CTGF was not identified. And then the gene expressions of ErbB4, CTGF and type X collagen were compared during regeneration from fractured bone through 35days in adult rat femurs to analyze the relationship between ErbB4 and CTGF. A hematoma was observed just after the femur was fractured and a callus was formed by mesenchymal stem cells derived from the bone marrow. After 7days, a callus was filled with every stages of chondrocytes and the gene expressions of CTGF were detected on hypertrophic chondrocytes in the callus. The gene expressions of CTGF and type X collagen have already finished after 35 days. Whereas, the gene expressions of ErbB4 and type X collagen began little late to the gene expression of CTGF on hypertrophic chondrocytes. Even the regeneration has finished, the gene expressions of ErbB4 could be detected on mesenchymal cells surrounded the regenerated area. These results indicate that the gene expressions of CTGF and ErbB4 take place on hypertrophic chondrocytes, therefore, CTGF may have certain relationship to ErbB4 in the skeletal development. In addition, the endochondral bone formation was took place normally in ErbB2 targeted mutants, however, there was no apoptotic figure in the calcification front of these mutants.