Vitamin D Increases Cellular Turnover and Functionally Restores the Skeletal Muscle after Crush Injury in Rats
The American Journal of Pathology] Dec 2012
Ioannis Stratos∗, †, Zhengdong Li∗, Philipp Herlyn∗, Robert Rotter∗, Ann-Kathrin Behrendt∗, Thomas Mittlmeier†, Brigitte Vollmar∗, ,
∗ Institute for Experimental Surgery, University of Rostock, Rostock, Germany
† Department of Trauma and Reconstructive Surgery, University of Rostock, Rostock, Germany
Insufficient skeletal muscle regeneration after injury often impedes the healing process and is accompanied by functional deficiencies or pain. The aim of our study was to provide evidence that vitamin D improves muscle healing after muscle injury. Therefore, we used male rats and induced an injury of the soleus muscle. After crush injury, animals received either 8.3 mg/kg (332,000 IU/kg) body weight vitamin D or vehicle solution, s.c. After assessment of muscle force at days 1, 4, 14, and 42 after injury, sampling of muscle tissue served for analysis of proliferation (5-bromo-2′-deoxyuridine IHC), apoptosis (ApopTag kit), satellite cells (paired-box protein 7 IHC), and prolyl-4-hydroxylase-β expression (Western blot analysis). Vitamin D application caused a significant increase in cell proliferation and a significant inhibition of apoptosis at day 4 after injury compared to control animals. The numbers of satellite cells were not influenced by the vitamin D application, but there was an increase in prolyl-4-hydroxylase-β expression, indicative of increased extracellular matrix proteins. This cellular turnover resulted in a faster recovery of contraction forces at day 42 in the vitamin D group. Current data support the hypothesis that vitamin D promotes the regenerative process in injured muscle. Thus, vitamin D treatment may represent a promising therapy to optimize recovery after injury.
332,000 IU/kg is a 1 / 2 the lethal dose of vitamin D
LD-50 (kills 50% of the rats) = 680,000 IU per kg