APC-Cdh1 Inhibits the Proliferation and Activation of Oligodendrocyte Precursor Cells after Mechanical Stretch Injury.

Abstract

The incidence of spinal cord injury (SCI) continues to increase; however, the involved mechanisms remain unclear. Anaphase promoting complex (APC) and its regulatory subunit Cdh1 play important roles in the growth, development, and repair of the central nervous system (CNS). Cdh1 is involved in the pathophysiological processes of neuronal apoptosis and astrocyte-reactive proliferation after ischemic brain injury, whereas the role played by APC-Cdh1 in the proliferation and activation of oligodendrocyte precursor cells (OPCs) after SCI remains unresolved. Using primary cultures of spinal oligodendrocyte precursor cells, we successfully established an in vitro mechanical stretch injury model to simulate SCI. Cell viability and proliferation were determined by MTT assay and flow cytometric analysis of the cell cycle. Real-time fluorescent quantitative PCR and Western blot analysis determined the mRNA and protein expression levels of Cdh1 and its downstream substrates Skp2 and Id2. Mechanical stretch injury decreased the proliferative activity of OPCs and enhanced cellular Cdh1 expression. Dampened expression of Cdh1 in primary OPCs significantly promoted proliferation and activation of OPCs after SCI. In addition, the expression of the downstream substrates of Cdh1, Skp2, and Id2 was decreased following mechanical injury, whereas adenovirus-mediated Cdh1 RNA interference increased postinjury expression of Skp2 and Id2. These findings suggest that APC-Cdh1 might be involved in regulating the proliferation and activation of OPCs after mechanical SCI. Moreover, degraded ubiquitination of the downstream substrates Skp2 and Id2 might play an important role, at least in part, in the beneficial effects of OPCs activity following SCI.