Contrasting effect of perlecan on adipogenic andosteogenic differentiation of mesenchymal stem cellsin vitro

摘要

Perlecan, a basement membrane component, shows diverse functions in different organs and tissues. However, the roleof perlecan in differentiation of mesenchymal stem cells (MSCs) has been barely investigated. In this study, we examinedthe effect of perlecan on adipogenic and osteogenic differentiation of MSCs in vitro by adding extrinsic perlecan to culturemedia or blocking the function of intrinsic perlecan expressed into culture media by differentiating MSCs. Extrinsic perlecansuppressed adipogenic differentiation; however, it promoted osteogenic differentiation. These functions were furtherconfirmed by a study of blocking intrinsic perlecan. Perlecan treated with heparitinase-I also showed the suppressive effecton adipogenic differentiation. In contrast, the promotive effect on osteogenic differentiation was found to be heparansulfate-dependent. Intrinsic perlecan was suggested to be effective at the late stage of adipogenic differentiation by astudy of perlecan-blocking performed at distinct periods, but was suggested to be effective at the early stage of osteogenicdifferentiation. Our results showed perlecan has contrasting effect on adipogenic and osteogenic differentiation of MSCsdue to its diverse actions. Based on these outcomes, we recognized that employing extrinsic perlecan or blocking intrinsicperlecan is effective for regulating adipogenic and osteogenic differentiation of MSCs by restricting its direction.