J. Kleinnulend et al., OSTEOGENIC PROTEIN (OP-1, BMP-7) STIMULATES CARTILAGE DIFFERENTIATIONOF HUMAN AND GOAT PERICHONDRIUM TISSUE IN-VITRO, Journal of biomedical materials research, 40(4), 1998, pp. 614-620
The objective of this study was to examine in vitro the influence of r
ecombinant human osteogenic protein-1 [rhOP-1, or bone morphogenetic p
rotein-7 (BMP-7)] on cartilage formation by human and goat perichondri
um tissue containing progenitor cells with chondrogenic potential. Fra
gments of outer ear perichondrium tissue were embedded in clotting aut
ologous blood to which rhOP-1 had been added or not added (controls),
and the resulting explant was cultured for 3 weeks without further add
ition of rhOP-1. Cartilage formation was monitored biochemically by me
asuring [S-35]-sulphate incorporation into proteoglycans and histologi
cally by monitoring the presence of metachromatic matrix with cells in
nests. The presence of rhOP-1 in the explant at the beginning of cult
ure stimulated [S-35]- sulphate incorporation into proteoglycans in a
dose-dependent manner after 3 weeks of culture. Maximal stimulation wa
s reached at 40 mu g/mL, (human explants: +148%; goat explants: +116%)
. Histology revealed that explants treated with 20-200 mu g/mL of rhOP
-1, but not untreated control explants, contained areas of metachromat
ic-staining matrix with chondrocytes in cell nests. It was concluded t
hat rhOP-1 stimulates differentiation of cartilage from perichondrium
tissue. The direct actions of rhOP-1 on perichondrium cells in the sti
mulation of chondrocytic differentiation and production of cartilage m
atrix in vitro provides a cellular mechanism for the induction of cart
ilage formation by rhOP-1 in vitro. Thus rhOP-1 may promote early step
s in the cascade of events leading to cartilage formation and could pr
ove to be an interesting factor in the regeneration of cartilage in ar
ticular cartilage defects. (C) 1998 John Wiley & Sons, Inc.