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

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


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Regeneration / genetics*
  • Calcification, Physiologic / genetics
  • Cell Differentiation / genetics
  • Cell Proliferation
  • Diabetes Mellitus, Experimental
  • Diabetes Mellitus, Type 2 / genetics*
  • Diabetes Mellitus, Type 2 / metabolism*
  • Disease Models, Animal
  • Gene Expression
  • Mice
  • Mice, Knockout
  • Myostatin / antagonists & inhibitors
  • Myostatin / genetics*
  • Osteogenesis / genetics*
  • Stem Cells / cytology
  • Stem Cells / metabolism


  • Mstn protein, mouse
  • Myostatin