Fig. 2
Genetic deletion of muscle RANK or selective inhibitions of RANKL or TRAIL in dystrophic mice. a Maximum specific force analysis of the Sol, EDL and Dia muscles were performed on 5-week-old C57BL/6, mdx-RANKmko, mdx-RANKf/f or mdx mice treated from days 25 to 35 with vehicle (PBS) or full-length OPG-Fc [1 mg/kg/d]. Uninjured muscles from C57BL/6 mice were used as controls. Full-length OPG-Fc [1 mg/kg/d] treatments and to a lesser extent, muscle-specific RANK deletion significantly preserved muscle force. b Schematic representations of full-length OPG-Fc, truncated OPG-Fc, RANKL and TRAIL antibodies. c Contractile properties of EDL muscles were performed on 5-week-old mdx mice treated from days 25 to 35 with anti-RANKL or/and anti-TRAIL antibodies or truncated OPG-Fc. The inhibition of RANKL and TRAIL for 10 days increased the force production of dystrophic EDL muscles by 45% and 17% respectively. The truncated OPG-Fc had similar effects than anti-RANKL, increasing the force production of EDL muscles by 43%, which were markedly lower than that of dystrophic EDL muscles from full-length OPG-Fc treated mdx mice (+ 162%). d To explore whether full-length OPG-Fc acts independently of RANKL/RANK, mdx-RANKmko mice were treated from days 25 to 35 with full-length OPG-Fc [1 mg/kg/d], and showed additional gain in force relative to PBS-treated mdx-RANKmko mice. The dotted line is the visual representation of full-length OPG-Fc data. Data are shown as mean +/− s.e.m., one way ANOVA and Tukey’s post-hoc tests; significantly different from PBS-treated mdx mouse; * p < 0.05, ** p < 0.01, *** p < 0.001