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. (24th July 2018)

• Record Type: Journal Article
• Authors: Betz, Volker M.; Ren, Bin; Messmer, Carolin; Jansson, Volkmar; Betz, Oliver B.; Müller, Peter E.
• Is Part Of: Journal of gene medicine. Volume 20:Number 9(2018)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2018-07-24
• Subjects: bone morphogenetic protein‐2 -- bone regeneration -- gene therapy -- heterodimers -- muscle tissue -- osteoinduction; Genetic transformation -- Periodicals; Gene Transfer -- Periodicals; Gene Therapy -- Periodicals; 616.042
• DOI: 10.1002/jgm.3042
• Languages: English
• ISSNs: 1099-498X

Abstract

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 20 days in normal medium, osteogenic medium or osteogenic medium supplemented with either a low (50 ng/ml) or high (200 ng/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. Conclusions: The 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.