Lack of caspase-3 attenuates immobilization-induced muscle atrophy and loss of tension generation along with mitigation of apoptosis and inflammation

Introduction: Immobilization by casting induces disuse muscle atrophy (DMA). Methods: Using wild type (WT) and caspase-3 knockout (KO) mice, we evaluated the effect of caspase-3 on muscle mass, apoptosis, and inflammation during DMA. Results: Caspase-3 deficiency significantly attenuated muscle mass decrease [gastrocnemius: 28 +/- 1% in KO vs. 41 +/- 3% in WT; soleus: 47 +/- 2% in KO vs. 56 +/- 2% in WT; (P < 0.05)] and gastrocnemius twitch tension decrease (23 +/- 4% in KO vs. 36 +/- 3% in WT, P < 0.05) at day 14 in immobilized vs. contralateral hindlimb. Lack of caspase-3 decreased immobilization-induced increased apoptotic myonuclei (3.2-fold) and macrophage infiltration (2.2-fold) in soleus muscle and attenuated increased monocyte chemoattractant protein-1 mRNA expression (2-fold in KO vs. 18-fold in WT) in gastrocnemius. Conclusions: Caspase-3 plays a key role in DMA and associated decreased tension, presumably by acting on the apoptosis and inflammation pathways. Muscle Nerve 47: 711721, 2013