Stimulation of proteoglycan synthesis in explants of porcine articular cartilage by recombinant osteogenic protein-1 (bone morphogenetic protein-7).
Osteogenic protein-1 (also known as bone morphogenetic protein-7) is a member of the bone morphogenetic protein family. Bone morphogenetic proteins and related members of the TGF-beta (transforming growth factor-beta) superfamily are involved in the development and repair of bone. Recombinant bone morphogenetic proteins induce the formation of new cartilage and bone at heterotopic sites. We investigated the influence of recombinant osteogenic protein-1 (at doses of three, ten, thirty, or 100 nanograms per milliliter) on the synthesis and release of proteoglycans and the maintenance of a steady-state concentration of proteoglycans in explants of porcine articular cartilage that were maintained in chemically defined serum-free medium. We found a dose-dependent stimulation of proteoglycan synthesis and a concurrent decrease in the rate of release of proteoglycans from the explants. The size of the proteoglycan monomers and the composition of the glycosaminoglycan chains in the untreated articular cartilage were similar to those in the articular cartilage treated with osteogenic protein-1. The capacity of the newly synthesized proteoglycan monomers to form aggregates with exogenous hyaluronic acid was found to be similar to that of proteoglycans in bovine nasal cartilage. Our results demonstrated that osteogenic protein-1 stimulated the synthesis of proteoglycans and diminished the release of proteoglycans from explants of porcine articular cartilage.


CONCLUSIONS
The maintenance and repair of articular cartilage is a formidable challenge in clinical orthopaedics. The stimulation of proteoglycan synthesis by osteogenic protein-1 (bone morphogenetic protein-7) in explants of cartilage maintained in chemically defined serum-free medium implies that recombinant osteogenic protein-1 may play a role in the maintenance of a steady-state concentration of proteoglycans in articular cartilage, a desirable prerequisite for optimum repair of cartilage. Osteogenic protein-1 can initiate the formation of cartilage from mesenchymal cells. Once new cartilage has formed at the site of repair, osteogenic protein-1 also may maintain the synthesis of proteoglycans.
Lietman
S A
SA
Department of Orthopaedic Surgery, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Yanagishita
M
M
Sampath
T K
TK
Reddi
A H
AH
D000818:Animals; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins / Q000494:pharmacology*; D002358:Cartilage, Articular / Q000187:drug effects / Q000378:metabolism*; D006025:Glycosaminoglycans / Q000032:analysis; D008297:Male; D011509:Proteoglycans / Q000096:biosynthesis*; D011994:Recombinant Proteins; D013552:Swine; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins; D006025:Glycosaminoglycans; D011509:Proteoglycans; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta