Format

Send to

Choose Destination
Sci Rep. 2017 Aug 29;7(1):9878. doi: 10.1038/s41598-017-10404-z.

Inhibition of GDF8 (Myostatin) accelerates bone regeneration in diabetes mellitus type 2.

Author information

1
Department of Plastic Surgery, BG University Hospital Bergmannsheil, Ruhr University Bochum, Bürkle-de-la-Camp Platz 1, 44789, Bochum, Germany.
2
Department of Plastic Surgery, BG University Hospital Bergmannsheil, Ruhr University Bochum, Bürkle-de-la-Camp Platz 1, 44789, Bochum, Germany. bjorn.behr@rub.de.

Abstract

Metabolic diseases like diabetes mellitus cause bone healing deficiencies. We found significant impairment of bone regeneration, osteogenic differentiation and proliferation in diabetic bone. Moreover recent studies suggest a highly underestimated importance of GDF8 (Myostatin) in bone metabolism. Our goal was to analyze the role of GDF8 as a regulator of osteogenic differentiation, proliferation and bone regeneration. We used a murine tibial defect model in diabetic (Leprdb-/-) mice. Myostatin-Inhibitor Follistatin was administered in tibial bony defects of diabetic mice. By means of histology, immunohistochemistry and QRT-PC osteogenesis, differentiation and proliferation were analyzed. Application of Myostatin-inhibitor showed a significant improvement in diabetic bone regeneration compared to the control group (6.5 fold, p < 0.001). Immunohistochemistry revealed a significantly higher proliferation (7.7 fold, p = 0.009), osteogenic differentiation (Runx-2: 3.7 fold, p = 0.011, ALP: 9.3 fold, p < 0.001) and calcification (4.9 fold, p = 0.024) in Follistatin treated diabetic animals. Therapeutical application of Follistatin, known for the importance in muscle diseases, plays an important role in bone metabolism. Diabetic bone revealed an overexpression of the catabolic protein Myostatin. Antagonization of Myostatin in diabetic animals leads to a restoration of the impaired bone regeneration and represents a promising therapeutic option.

PMID:
28852138
PMCID:
PMC5575348
DOI:
10.1038/s41598-017-10404-z
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center