Abstract
Background: Multiple sclerosis (MS) is an autoimmune and neurodegenerative pathology characterised by demyelinated plaques in the CNS. Remyelination is an active repair process involving oligodendrocyte precursor cells (OPCs) proliferation and differentiation. It is positively correlated with slower progression of MS and a prolonged survival of MS patients. With time, tissue remodelling becomes less and less effective, leading to a glial scar and to neurodegeneration. Previously, we identified an increased Chitinase 3-like protein1 (CHI3L1) and Syndecan-1 (SDC1) expression in cerebrospinal fluid (CSF) as prognostic biomarkers of MS. CHI3L1 is a secreted protein involved in extracellular matrix remodelling and commonly expressed during inflammation. On the other hand, SDC1 is a widely expressed transmembrane protein involved in cell-matrix interactions. In other pathologies such as cancer, CHI3L1 and SDC1 interaction has already been described to play a role in proliferation, adhesion, migration and differentiation processes. Finally, in human brain, we observed an important expression of CHI3L1 by astrocytes and of SDC1 by glial cells within MS plaques. However, the role of CHI3L1 and SDC1 in demyelination and remyelination is largely unknown. Here, we aim to analyse the influence of CHI3L1 and SDC1 possible interaction on proliferation, differentiation and migration of OPCs.Methods: First, we exposed primary cell cultures of rat OPCs to recombinant human CHI3L1 (rhCHI3L1) to explore CHI3L1 impact on OPCs processes by microscopy. We monitored OPCs proliferation by EDU labelling, OPCs differentiation using maturation markers (NG2, O4) by immunolabelling and OPCs migration by agarose drop assay. We analysed SDC1 timing expression during OPCs differentiation by immunolabelling.Results: In primary cell culture, we did not observed any impact of rhCHI3L1 on OPCs proliferation., Cell migration was slightly increased by exposure to rhCHI3L1. We observed an increase of NG2+ cells and a decrease of O4+ cells in rhCHI3L1 condition, suggesting that rhCHI3L1 had a transient impact on OPCs differentiation in vitro. Moreover, O4+ cells expressed the majority of SDC1 in OPCs primary cell culture.Discussion: OPCs migration occurring during early stages of differentiation, the increase observed could be a direct effect of CHI3L1 or a side effect of the differentiation slow down effect of CHI3L1. We also demonstrate a strong SDC1 expression in early OPC stages of differentiation. The timing of rhCHI3L1 effects and SDC1 expression support a possible interaction between these two MS biomarkers in OPCs. Next step will be to study the CHI3L1 and SDC1 interaction in OPCs at early stages of differentiation and the pathway(s) involved.