Hm. Vanbeuningen et al., DIFFERENTIAL-EFFECTS OF LOCAL APPLICATION OF BMP-2 OR TGF-BETA-1 ON BOTH ARTICULAR-CARTILAGE COMPOSITION AND OSTEOPHYTE FORMATION, Osteoarthritis and cartilage, 6(5), 1998, pp. 306-317
Objective: The related molecules bone morphogenetic protein-2 (BMP-2)
and transforming growth factor beta-1 (TGF-beta 1) have both been show
n to stimulate chondrocyte proteoglycan (PG) synthesis in vitro. We in
vestigated the in-vivo effects of these factors on articular cartilage
PG metabolism. Design: Several doses of BMP-2 or TGF-beta 1 were inje
cted into the murine knee joint, once or repeatedly. Patellar cartilag
e PG synthesis it-as measured by [S-35]-sulfate incorporation and reve
rse transcriptase polymerase chain reaction (RT-PCR). PG content was a
nalyzed by measuring safranin O staining intensity on histologic secti
ons. Results: A single injection of 200 ng BMP-X induced a much earlie
r and more impressive stimulation of articular cartilage PG synthesis,
than 200 ng TGF-beta 1. RT-PCR revealed that both factors upregulated
mRNA of aggrecan more than that of biglycan and decorin. However, 21
days after a single injection of 200 ng TGF-beta 1 PG synthesis still
was significantly increased, while stimulation by BMP-2 only lasted fo
r 3 to ii days. Stimulation by BMP-2 could be prolonged to at least 2
weeks by triple injections of 200 ng each, at alternate days. Remarkab
ly, even after this intense exposure to BMP-2, stimulation of PG synth
esis was not reflected in long-lasting enhancement of PG content of ar
ticular cartilage. In contrast, even a single injection with 200 ng of
TGF-beta 1 induced prolonged enhancement of PCT content. After repeat
ed injections, both BMP-2 and TGF-beta 1 induced chondrogenesis at spe
cific sites. 'Chondrophytes' induced by BMP-2 were found predominantly
in the region where the growth plates meet the joint space, while tho
se triggered by TGF-beta 1 originated from the periosteum also at site
s remote from the growth plates. Conclusions: BMP-2 and TGF-beta stimu
late PG synthesis and PG content with differ ent kinetics, and these f
actors have different chondro-inductive properties.