Inhibition of TROY promotes OPC differentiation and increases therapeutic efficacy of OPC graft for spinal cord injury

Objective:To observe the regulatory effects of TROY on neural myelination in central nervous system(CNS)and remyelination in response to spinal cord injury(SCI)by oligodendrocyte precursor cell(OPC).Results:TROY expression was detected by RT-PCR and Western blotting in OPCs as well as in differentiated premature and mature oligodendrocytes of postnatal mice.Pharmacological inhibition or RNAi-induced knockdown of TROY promotes OPC differentiation,whereas overexpression of TROY dampens oligodendrocyte maturation.Furthermore,treatment of co-cultures of DRG neurons and OPCs with TROY inhibitors promotes myelination and myelin sheath-like structures.Mechanically,protein kinase C(PKC)signaling is involved in the regulation of the inhibitory effects of TROY.Moreover,in situ transplantation of OPCs with TROY knockdown leads to notably enhanced remyelination as well as augmented recovery of motor function and nervous conduction in rats with SCI.Conclusions:Our results indicate that TROY negatively modulates remyelination in the CNS,and thus may be a suitable target for improving the therapeutic efficacy of cell transplantation for CNS injury.