BMP-2 and BMP-9 promotes chondrogenic differentiation of human multipotential mesenchymal cells and overcomes the inhibitory effect of IL-1.
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-1beta 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.
Majumdar
M K
MK
Genetics Institute, Inc., Cambridge, Massachusetts 02140, USA. mmajumdar@genetics.com
Wang
E
E
Morris
E A
EA
D053674:Aggrecans; D015415:Biomarkers / Q000032:analysis; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000494:pharmacology*; D002454:Cell Differentiation; D002478:Cells, Cultured; D019902:Chondrocytes / Q000502:physiology*; D020219:Chondrogenesis; D024043:Collagen Type II / Q000096:biosynthesis / Q000235:genetics; D004336:Drug Antagonism; D016326:Extracellular Matrix Proteins; D055427:Growth Differentiation Factor 2; D055412:Growth Differentiation Factors; D006609:High Mobility Group Proteins / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D007700:Kinetics; D037181:Lectins, C-Type; D008648:Mesoderm / Q000502:physiology*; D011509:Proteoglycans / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D055758:SOX9 Transcription Factor; D013234:Stem Cells / Q000187:drug effects / Q000502:physiology; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics; D016212:Transforming Growth Factor beta
D053674:Aggrecans; C525718:BMP2 protein, human; D015415:Biomarkers; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D024043:Collagen Type II; D016326:Extracellular Matrix Proteins; C525887:GDF2 protein, human; D055427:Growth Differentiation Factor 2; D055412:Growth Differentiation Factors; D006609:High Mobility Group Proteins; D007375:Interleukin-1; D037181:Lectins, C-Type; D011509:Proteoglycans; D012333:RNA, Messenger; D055758:SOX9 Transcription Factor; C527932:SOX9 protein, human; D014157:Transcription Factors; D016212:Transforming Growth Factor beta