Effect of BMP-2 and BMP-7 homodimers and a mixture of BMP-2/BMP-7 homodimers on osteoblast adhesion and growth following culture on a collagen scaffold.
In the present study, we studied the involvement of BMP-2 and BMP-7 as homodimers and as a mixture of homodimers in bone regeneration using an engineered bone model. The engineered bone model consisted of a collagen scaffold populated with osteoblasts that acted as a carrier for the BMPs. BMP-2, BMP-7 and a mixture of BMP-2/BMP-7 were used at final concentrations of 10 and 100 ng ml(-1). Osteoblasts seeded onto a collagen scaffold were cultured for 24 h before being stimulated with the BMPs. Four days later, osteoblast adhesion to and growth on the scaffold were assessed. Osteocalcin, IL-6, metalloproteinase (MMP-2 and MMP-9) and protease inhibitor (TIMP-1 and TIMP-2) mRNA and protein levels were measured. Our results showed that the BMP-2, BMP-7 and a mixture of BMP-2/BMP-7 all promoted osteoblast growth on the collagen scaffold, with the mixture of BMP-2/BMP-7 enhancing the most growth. BMP-2 and the mixture of BMP-2/BMP-7 enhanced osteocalcin (an osteoblast differentiation marker) mRNA expression and protein secretion, likely via the IL-6 pathway given that IL-6 secretion was upregulated by BMP-7 and a mixture of BMP-2/BMP-7. BMPs promote extracellular matrix production by inhibiting MMP-2 mRNA and increasing TIMP-1 and TIMP-2 mRNA expressions and protein secretions. BMP-2, BMP-7 and the mixture of BMP-2/BMP-7 could promote bone regeneration via different mechanisms involving IL-6 and MMP inhibitors.
Laflamme
Claude
C
Groupe de recherche en écologie buccale, Faculté de médecine dentaire, Université Laval, Québec City, Québec G1K 7P4, Canada.
Rouabhia
Mahmoud
M
D055396:Bone Morphogenetic Protein 2; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins / Q000008:administration & dosage* / Q000737:chemistry; D002448:Cell Adhesion / Q000187:drug effects; D018929:Cell Culture Techniques / Q000379:methods; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D003094:Collagen / Q000737:chemistry*; D019281:Dimerization; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D006801:Humans; D008422:Materials Testing; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D023822:Tissue Engineering / Q000379:methods*; D016212:Transforming Growth Factor beta / Q000008:administration & dosage* / Q000737:chemistry
C525718:BMP2 protein, human; C525819:BMP7 protein, human; D055396:Bone Morphogenetic Protein 2; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins; D004338:Drug Combinations; D016212:Transforming Growth Factor beta; D003094:Collagen