Mesenchymal stem cells (MSCs) are able to differentiate into many types of cells including chondrocytes. Transforming growth factor betal (TGF-betal) is very important in the regulation of chondrogenesis. Since cartilage-derived morphogenetic protein-1 (CDMP-1) belongs to the TGF-beta superfarnily, we tested whether CDMP-1 plays any role in the regulation of the differentiation of MSCs into chondrocytes using a high density pellet culture system. Based on the histological staining of glycosaminogly can using toluidine blue dye-binding method we found that CDMP-1 could initiate chondrogenic differentiation of MSCs as did TGF-betal. However. CDMP-1 was less stimulatory than TGF-betal. The combination of CDMP-1 and TGF-betal synergically induced chondrogenesis of MSCs. This synergic chondrogenic effect of CDMP-1 together with TGF-betal was further confirmed by quantification of GAG using dimethylinethylene blue dye-binding assay and immunohistochemical analysis of the expression of cartilage-specific protein collagen II. This study may provide an improved induction approach using MSCs for repairing damaged cartilage. (C) 2004 Elsevier Inc. All rights reserved.