Injury leads to release of endogenous molecules from damaged or necrotic cells. These molecules are termed DAMPs, and especially have attracted attention in the context of involvement of inflammation because DAMPs are known to act on several immune cells to trigger inflammatory response. Demyelination is common feature of central nervous system (CNS) disorders, and myelin repair is one of the promising therapeutic avenues in the field of myelin disorders. Myelin repair is mediated by proliferation of oligodendrocyte precursor cells (OPCs). In this study, we examined the role of DAMPs in OPC proliferation in vitro.
We cultured OPC cell line FBD-102b, which was established from fetal brain of p53-deficient mice. To mimic damaged cells, we prepared the brain extract from adult mouse. Cell proliferation was assessed by measurement of 5'-Bromo-2-deoxyuridine (BrdU) incorporation into FBD-102b. Treatment of FBD-102b with brain extract increased BrdU incorporation into FBD-102b, suggesting that DAMPs promotes OPC proliferation. We examined what kind of substance is involved in brain extract-mediated OPC proliferation. Brain extract was preincubated with pronase for protein degradation, and then this extract was added into the culture. Treatment with pronase-treated brain extract partially inhibited cell proliferation of FBD-102b, suggesting that protein in brain extract is involved in OPC proliferation. These results suggest that DAMPs have a potential to promote OPC proliferation, and identification of key molecule in DAMPs provides molecular target for treating demyelinating diseases.