Recombinant human osteogenic protein 1 is a potent stimulator of the synthesis of cartilage proteoglycans and collagens by human articular chondrocytes.
OBJECTIVE
To study the effects of recombinant human osteogenic protein-1 (rHuOP-1; bone morphogenetic protein-7) on proteoglycan and collagen synthesis by human articular chondrocytes.


METHODS
Articular chondrocytes from fetal, adolescent, and adult human donors were cultured in alginate beads for 4 days in a mixture of Ham's F-12, Dulbecco's modified Eagle's medium, 10% fetal bovine serum (FBS), then for an additional 3-10 days in the presence and absence of rHuOP-1, with and without FBS. Chondrocyte synthetic activity was measured as the amount of incorporation of 35S-sulfate into proteoglycans and 3H-proline into hydroxyproline. Sieve chromatography and sodium dodecyl sulfate-polyacrylamide gel electrophoresis were performed to identify specific proteoglycans and collagens.


RESULTS
Recombinant human OP-1 markedly stimulated the synthesis of proteoglycans (mostly aggrecan) and collagens (predominantly type II) by all chondrocyte preparations. This did not require the presence of FBS and was associated with continued expression of the chondrocyte phenotype.


CONCLUSIONS
Recombinant human OP-1 is a more potent stimulator of the synthesis of cartilage-specific molecules by human articular chondrocytes than are other factors tested for comparison, including TGF beta 1 and activin A.
Flechtenmacher
J
J
Rush Medical College, Rush-Presbyterian-St. Luke's Medical Center, Chicago, Illinois, USA.
Huch
K
K
Thonar
E J
EJ
Mollenhauer
J A
JA
Davies
S R
SR
Schmid
T M
TM
Puhl
W
W
Sampath
T K
TK
Aydelotte
M B
MB
Kuettner
K E
KE
D028341:Activins; D000293:Adolescent; D000328:Adult; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins / Q000494:pharmacology*; D002356:Cartilage / Q000737:chemistry; D002358:Cartilage, Articular / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D002675:Child, Preschool; D003094:Collagen / Q000096:biosynthesis*; D005260:Female; D005333:Fetus / Q000166:cytology; D006801:Humans; D007231:Infant, Newborn; D007265:Inhibins / Q000494:pharmacology; D008297:Male; D011509:Proteoglycans / Q000096:biosynthesis*; D011994:Recombinant Proteins / Q000494:pharmacology; D013462:Sulfur Radioisotopes; D016212:Transforming Growth Factor beta / Q000494:pharmacology
C525819:BMP7 protein, human; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins; D011509:Proteoglycans; D011994:Recombinant Proteins; D013462:Sulfur Radioisotopes; D016212:Transforming Growth Factor beta; D028341:Activins; D007265:Inhibins; D003094:Collagen