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Betz, Volker M.; Ren, Bin; Messmer, Carolin; Jansson, Volkmar; Betz, Oliver B.; Müller, Peter E. (2018): Bone morphogenetic protein-2 is a stronger inducer of osteogenesis within muscle tissue than heterodimeric bone morphogenetic protein-2/6 and-2/7: Implications for expedited gene-enhanced bone repair. In: Journal of Gene Medicine, Vol. 20, No. 9, e3042
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Abstract

Background: Bone morphogenetic protein (BMP)-2 gene-activated muscle tissue fragments can regenerate large bone defects in preclinical animal models. The use of tissue fragments instead of isolated cells expedites gene-enhanced tissue engineering and may increase the possibility of clinical translation. The present in vitro study investigated whether the osteoinductive effect of BMP-2 on muscle tissue fragments can be enhanced using the heterodimers BMP-2/6 or BMP-2/7. Methods: Skeletal muscle tissue fragments from rats were cultured in vitro for up to 20days in normal medium, osteogenic medium or osteogenic medium supplemented with either a low (50ng/ml) or high (200ng/ml) concentration of recombinant human BMP-2, BMP-2/6 or BMP-2/7. Osteoinduction was evaluated by a quantitative reverse transcriptase-polymerase chain reaction, Alizarin red S staining, immunohistology and histomorphometry. Results: Interestingly, BMP-2 was a significantly stronger inducer of osteogenic differentiation within muscle tissue than both heterodimers. Even the low concentration of BMP-2 elicited significantly higher levels of calcium deposition, bone-specific gene expression and protein production than the high concentration of both heterodimers. At the high concentration, BMP-2/7 had a significantly stronger osteogenic effect on muscle than BMP-2/6. Conclusion: sThe homodimer BMP-2 induced osteoblastogenesis in muscle faster, at a lower concentration and with a higher potency than the heterodimers BMP-2/6 or BMP-2/7. The findings of this in vitro study encourage bone repair by muscle implants in combination with BMP-2 single growth factor delivery, which might be beneficial with respect to clinical translation.