BMP-2 and BMP-9 promote chondrogenic differentiation of human multipotential mesenchymal cells and overcome the inhibitory effect of IL-1

Bone morphogenetic proteins play important roles in connective tissue morph ogenesis. In this study, we used human multipotential mesenchymal cells as a target to analyze the effect of bone morphogenetic proteins on chondrogen esis. We also analyzed the effect of proinflammatory cytokine interleukin-1 on chondrogenic-differentiated cells and the interaction of IL-1 beta with bone morphogenetic proteins. Cells placed in a 3-dimensional matrix of alg inate beads and cultured in a serum-free media with bone morphogenetic prot ein-2 and -9 induced expression of type II collagen (Col2A1) mRNA and incre ased expression of aggrecan and cartilage oligomeric matrix protein suggest ing chondrogenic differentiation of the cells. The transcription factor Sox -9 that regulates both Col2A1 and aggrecan gene expression showed increased expression with BMP treatment. Chondrogenic differentiated cells treated w ith interleukin-1 decreased Sox-9, Col2A1 and aggrecan gene expression. Rem oval of interleukin-1 and further addition of bone morphogenetic proteins r esulted in returned expression of chondrogenic markers. Chondrogenic differ entiated cells cultured in the presence of different concentrations of bone morphogenetic proteins and interleukin-1 showed that bone morphogenetic pr oteins were able to partially block the suppressive effect of interleukin-1 . This study shows that bone morphogenetic proteins play an important role in chondrogenesis and may prove to be potential therapeutics in cartilage r epair. (C) 2001 Wiley-Liss, Inc.