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

• Published in: Journal of cellular physiology Vol. 189; no. 3; pp. 275 - 284
• Main Authors: Majumdar, Manas Kumar, Wang, Eunice, Morris, Elisabeth Ann
• Format: Journal Article
• Language: English
• Published: New York John Wiley & Sons, Inc 01.12.2001
• Subjects: Aggrecans; Biomarkers - analysis; Bone Morphogenetic Protein 2; Bone Morphogenetic Proteins - pharmacology; Cell Differentiation; Cells, Cultured; Chondrocytes - physiology; Chondrogenesis; Collagen Type II - biosynthesis; Collagen Type II - genetics; Drug Antagonism; Extracellular Matrix Proteins; Growth Differentiation Factor 2; Growth Differentiation Factors; High Mobility Group Proteins - biosynthesis; High Mobility Group Proteins - genetics; Humans; Interleukin-1 - pharmacology; Kinetics; Lectins, C-Type; Mesoderm - physiology; Proteoglycans - biosynthesis; Proteoglycans - genetics; RNA, Messenger - biosynthesis; SOX9 Transcription Factor; Stem Cells - drug effects; Stem Cells - physiology; Transcription Factors - biosynthesis; Transcription Factors - genetics; Transforming Growth Factor beta
• ISSN: 0021-9541; 1097-4652
• DOI: 10.1002/jcp.10025

Bone morphogenetic proteins play important roles in connective tissue morphogenesis. In this study, we used human multipotential mesenchymal cells as a target to analyze the effect of bone morphogenetic proteins on chondrogenesis. We also analyzed the effect of proinflammatory cytokine interleukin‐1 on chondrogenic‐differentiated cells and the interaction of IL‐1β with bone morphogenetic proteins. Cells placed in a 3‐dimensional matrix of alginate beads and cultured in a serum‐free media with bone morphogenetic protein‐2 and ‐9 induced expression of type II collagen (Col2A1) mRNA and increased expression of aggrecan and cartilage oligomeric matrix protein suggesting 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 with interleukin‐1 decreased Sox‐9, Col2A1 and aggrecan gene expression. Removal of interleukin‐1 and further addition of bone morphogenetic proteins resulted in returned expression of chondrogenic markers. Chondrogenic differentiated cells cultured in the presence of different concentrations of bone morphogenetic proteins and interleukin‐1 showed that bone morphogenetic proteins 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 repair. © 2001 Wiley‐Liss, Inc.