Enhanced tenogenic differentiation and tendon-like tissue formation by CHIP overexpression in tendon-derived stem cells

摘要

The carboxyl terminus of Hsc70-interacting protein (CHIP,also known as STUB1) plays critical roles in the proliferation and differentiation of many types of cells.The potential function of CHIP in tendon-derived stem cells (TDSCs) remains largely unknown at present.Here,we investigated the effects of CHIP on tenogenic differentiation of TDSCs via lentivirus-mediated overexpression.Forced expression of CHIP induced morphological changes and significantly enhanced cell proliferation,as well as tendon differentiation in vitro.Upon stimulation with differentiation induction medium,CHIP-overexpressing TDSCs displayed significant inhibition of differentiation into osteogenic and adipogenic lineages.Subsequent implantation of TDSCs overexpressing CHIP with collagen sponges into nude mice induced a marked increase in ectopic tendon formation in vivo,compared with the control group.Our findings collectively suggest that CHIP is an important contributory factor to tenogenic tissue formation.