Recombinant osteogenic protein-1 upregulates extracellular matrix metabolism by rabbit annulus fibrosus and nucleus pulposus cells cultured in alginate beads.
This study was performed to determine if recombinant human osteogenic protein-1 (rhOP-1) is effective in promoting matrix synthesis and matrix formation by rabbit nucleus pulposus (NP) and annulus fibrosus (AF) cells cultured in alginate beads. The effects of culturing the cells in the presence of various concentrations of rhOP-1 were assessed by measuring changes in cell proliferation, proteoglycan (PG) and collagen synthesis and mRNA expression, and in the matrix contents of PG and collagen, as indicators of matrix accumulation. At high concentrations, rhOP-1 had a moderate mitogenic effect on both NP and AF cells. It also stimulated the synthesis of PG and collagen in a dose-dependent manner: this was associated with a corresponding increase in the expression of mRNA for aggrecan core protein and collagen type II. The stimulatory effect of rhOP-1 on PG synthesis was more pronounced than that on collagen synthesis. Continuous treatment with rhOP-1 led to an increase in the total DNA, PG and collagen contents in both NP and AF cultures. The results presented here provide evidence of the ability of rhOP-1 to stimulate the metabolism of both rabbit AF and NP cells cultured in alginate beads.
Masuda
K
K
Departments of Orthopedic Surgery and Biochemistry, Rush Medical College at Rush-Presbyterian-St. Luke's Medical Center, 1653 W. Congress Parkway, Chicago, IL 60612, USA. kmasuda@rush.edu
Takegami
K
K
An
H
H
Kumano
F
F
Chiba
K
K
Andersson
G B J
GB
Schmid
T
T
Thonar
E
E
D053674:Aggrecans; D000464:Alginates; D000818:Animals; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins / Q000494:pharmacology*; D002452:Cell Count; D002470:Cell Survival; D002478:Cells, Cultured; D003094:Collagen / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism*; D016326:Extracellular Matrix Proteins; D006801:Humans; D007403:Intervertebral Disc / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D037181:Lectins, C-Type; D008863:Microspheres; D010641:Phenotype; D011509:Proteoglycans / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D011817:Rabbits; D011994:Recombinant Proteins / Q000494:pharmacology; D016212:Transforming Growth Factor beta; D015854:Up-Regulation
D053674:Aggrecans; D000464:Alginates; C525819:BMP7 protein, human; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins; D016326:Extracellular Matrix Proteins; D037181:Lectins, C-Type; D011509:Proteoglycans; D012333:RNA, Messenger; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; D003094:Collagen; D004247:DNA