Bone morphogenetic protein 9 is a potent anabolic factor for juvenile bovine cartilage, but not adult cartilage.
Members of the bone morphogenetic protein (BMP) group of the TGF-beta superfamily have been shown to enhance matrix synthesis and maintain cartilage phenotype in long-term culture. These proteins have also been shown to augment cartilage repair in vivo, and may be of potential therapeutic benefit in the treatment of damaged articular cartilage. The present study was undertaken to examine the effects of BMP-9 on the metabolism of juvenile and adult bovine cartilage in vitro, and to compare the effects to those produced by two previously characterized BMPs: BMP-2 and 13 (CDMP-2). BMP-9 lead to a 7-8-fold stimulation of proteoglycan synthesis at the highest concentration tested, and a 6.4-fold stimulation of collagen synthesis at a concentration of 50 ng/mL in juvenile cartilage. BMP-2 also lead to a 7-8-fold increase in proteoglycan synthesis at the highest concentration tested, and was able to induce collagen synthesis 6.4-fold, but at a concentration of 1000 ng/mL. Proteoglycans isolated from BMP-9 treated cartilage exhibited an increased hydrodynamic size possibly due to increased glycosaminoglycan substitution or decreased C-terminal proteolysis. Consistent with the idea of limited C-terminal proteolysis, BMP-9 treatment lead to a significant reduction in the turnover rate of proteoglycans in juvenile explants. Interestingly, all three BMPs were unable to induce a measurable anabolic response in adult cartilage explants.
Hills
Robert L
RL
Wyeth Inc., Cambridge, MA 02140, USA. robert.1.hills@pfizer.com
Belanger
Leona M
LM
Morris
Elisabeth A
EA
D000367:Age Factors; D000818:Animals; D055396:Bone Morphogenetic Protein 2; D052004:Bone Morphogenetic Protein Receptors; D019485:Bone Morphogenetic Proteins / Q000494:pharmacology*; D002356:Cartilage / Q000187:drug effects* / Q000378:metabolism; D002417:Cattle; D055427:Growth Differentiation Factor 2; D011509:Proteoglycans / Q000096:biosynthesis; D017978:Receptors, Growth Factor / Q000032:analysis; D016212:Transforming Growth Factor beta / Q000494:pharmacology
D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D055427:Growth Differentiation Factor 2; D011509:Proteoglycans; D017978:Receptors, Growth Factor; D016212:Transforming Growth Factor beta; D052004:Bone Morphogenetic Protein Receptors