Human bone marrow-derived stromal cells (hBMSC) are multi-potent stem cells that can differentiate into osteogenic and adipogenic lineages. Adiponectin (APN) is an adipocyte-derived hormone that modulates a series of metabolic processes. Recent studies revealed a relationship between APN and bone regeneration, though the underlying mechanism was not fully examined. Phosphatase and tensin homolog deleted on chromosome ten (PTEN) is a tumor suppressor and a therapeutic target for the metabolic syndrome. Its deletion mutants increase osteoblast activity and bone mineral density. Both APN and PTEN are involved in osteogenic differentiation. However, whether PTEN is involved in APNinduced bone metabolism remains unclear. This project was designed to study whether PTEN was involved in APN-mediated osteogenesis of hBMSCs. We found that APN downregulated PTEN expression and that both it and an inhibitor of PTEN (SF1670) increased the expression of osteogenic markers such as osteocalcin, alkaline phosphatase, and runt-related transcription factor-2 in APN-treated hBMSCs. Our results suggested that APN enhanced osteogenic differentiation of hBMSCs in vitro partially by inhibiting PTEN expression. APN could be a therapeutic agent in tissue regeneration engineering and bone regeneration by inhibiting PTEN expression and then promoting the osteogenic differentiation of hBMSCs. (C)16 Elsevier Inc. All rights reserved.