Osteogenic protein (OP-1, BMP-7) stimulates cartilage differentiation of human and goat perichondrium tissue in vitro.
The objective of this study was to examine in vitro the influence of recombinant human osteogenic protein-1 [rhOP-1, or bone morphogenetic protein-7 (BMP-7)] on cartilage formation by human and goat perichondrium tissue containing progenitor cells with chondrogenic potential. Fragments of outer ear perichondrium tissue were embedded in clotting autologous blood to which rhOP-1 had been added or not added (controls), and the resulting explant was cultured for 3 weeks without further addition of rhOP-1. Cartilage formation was monitored biochemically by measuring [35S]-sulphate incorporation into proteoglycans and histologically by monitoring the presence of metachromatic matrix with cells in nests. The presence of rhOP-1 in the explant at the beginning of culture stimulated [35S]-sulphate incorporation into proteoglycans in a dose-dependent manner after 3 weeks of culture. Maximal stimulation was reached at 40 microg/mL (human explants: +148%; goat explants: +116%). Histology revealed that explants treated with 20-200 microg/mL of rhOP-1, but not untreated control explants, contained areas of metachromatic-staining matrix with chondrocytes in cell nests. It was concluded that rhOP-1 stimulates differentiation of cartilage from perichondrium tissue. The direct actions of rhOP-1 on perichondrium cells in the stimulation of chondrocytic differentiation and production of cartilage matrix in vitro provides a cellular mechanism for the induction of cartilage formation by rhOP-1 in vivo. Thus rhOP-1 may promote early steps in the cascade of events leading to cartilage formation and could prove to be an interesting factor in the regeneration of cartilage in articular cartilage defects.
Klein-Nulend
J
J
ACTA-Vrije Universiteit, Department of Oral Cell Biology, Amsterdam, The Netherlands. J.Klein_Nulend.OCB.ACTA@med.vu.nl
Louwerse
R T
RT
Heyligers
I C
IC
Wuisman
P I
PI
Semeins
C M
CM
Goei
S W
SW
Burger
E H
EH
D000818:Animals; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins / Q000494:pharmacology*; D002356:Cartilage / Q000166:cytology* / Q000187:drug effects*; D002454:Cell Differentiation / Q000187:drug effects; D046508:Culture Techniques; D004431:Ear, External / Q000098:blood supply; D005260:Female; D006041:Goats; D006801:Humans; D016212:Transforming Growth Factor beta; D014945:Wound Healing / Q000187:drug effects
C525819:BMP7 protein, human; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins; D016212:Transforming Growth Factor beta