Stimulation of cartilage differentiation by osteogenic protein-1 in cultures of human perichondrium.
Exposure of progenitor cells with chondrogenic potential to recombinant human osteogenic protein-1 [rhOP-1, or bone morphogenetic protein-7 (BMP-7] may be of therapeutic interest in the regeneration of articular cartilage. Therefore, in this study, we examined the influence of rhOP-1 on cartilage formation by human perichondrium tissue containing progenitor cells with chondrogenic potential in vitro. Fragments of outer ear perichondrium tissue were embedded in clotting autologous blood to which rhOP-1 had been added or not (controls), and the resulting explant was cultured for 3 weeks without further addition of rhOP-1. Cartilage formation was monitored biochemically by measuring [&sup35;S]sulfate 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 [&sup35;S]sulfate incorporation into proteoglycans in a dose-dependent manner after 3 weeks of culture. Maximal stimulation was reached at 40 microgram/ml. Histology revealed that explants treated with 20-200 microgram/ml rhOP-1, but not untreated control explants, contained areas of metachromatic-staining matrix with chondrocytes in cell nests. These results suggest that rhOP-1 stimulates differentiation of cartilage from perichondrium tissue. The direct actions of rhOP-1 on perichondrium cells to stimulate chondrocytic differentiation and production of cartilage matrix in vitro provide 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. Therefore, rhOP-1 could be an interesting factor for regeneration of cartilage in articular cartilage defects.
Klein-Nulend
J
J
Department of Oral Cell Biology, ACTA-Vrije Universiteit, 1081 BT Amsterdam, The Netherlands.
Semeins
C M
CM
Mulder
J W
JW
Winters
H A
HA
Goei
S W
SW
Ooms
M E
ME
Burger
E H
EH
D000293:Adolescent; D000328:Adult; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins / Q000494:pharmacology*; D002356:Cartilage / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D002452:Cell Count; D002454:Cell Differentiation / Q000187:drug effects; D002648:Child; D004431:Ear, External / Q000166:cytology; D005260:Female; D006025:Glycosaminoglycans / Q000096:biosynthesis; D006801:Humans; D009924:Organ Culture Techniques; D011993:Recombinant Fusion Proteins / Q000494:pharmacology; D016212:Transforming Growth Factor beta
C525819:BMP7 protein, human; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins; D006025:Glycosaminoglycans; D011993:Recombinant Fusion Proteins; D016212:Transforming Growth Factor beta