Figure 4

S1P promotes functional improvement of mdx ( C57BL/10ScSn-Dmd^mdx/J) muscle. ( A ) Experimental schematic of longer-term, 14-day treatment of THI or PBS (vehicle) following CTX injury. THI was administered following the aforementioned dose and injection regimen. Following treatment, EDL muscles were harvested and specific isometric force was analyzed by in vitro myography from both injured and uninjured limbs. ( B ) Force frequency analysis reveals that EDL muscles isolated from injured limbs of THI-treated animals (n = 10) have significantly greater specific force compared to injured vehicle controls (n = 9). ( C ) Analysis of untreated and uninjured wt (C57BL/10ScSn) and mdx (C57BL/10ScSn-Dmd^mdx/J) indicate specific force improved in injured but not uninjured THI-treated EDL muscles. ( D ) Incubation of uninjured and untreated mdx (C57BL/10ScSn-Dmd^mdx/J) EDL muscles with a high concentration of S1P (10 μM) leads to a significant increase in maximal specific force. *P <0.05, **P <0.005 by student’s t-test. Error bars represent SEM. CTX, cardiotoxin; EDL, extensor digitorum longus; S1P, sphingosine-1-phoshate; SEM, standard error of the mean; THI, 2-acetyl-4(5)-tetrahydroxybutyl imidazole; wt, wild type.