Transforming growth factor-beta 1 stimulates articular chondrocyte proteoglycan synthesis and induces osteophyte formation in the murine knee joint.
BACKGROUND
High concentrations of active transforming growth factor-beta (TGF-beta) have been found in synovial fluids from arthritic joints. TGF-beta stimulates articular cartilage proteoglycan synthesis and suppresses proteoglycan degradation in vitro. In an earlier study, we found no effect on cartilage proteoglycan metabolism shortly after a single intra-articular injection of TGF-beta 1. In the present study, we used multiple intra-articular injections and a longer time-scale.


METHODS
TGF-beta 1 was injected into the murine knee joint to gain insight in the consequences of its overproduction in joint diseases. This was evaluated using histologic sections of the whole knee joint and measurements of articular cartilage proteoglycan synthesis and content.


RESULTS
At 6 hours after a single TGF-beta 1 injection, recruitment of polymorphonuclear leukocytes (PMNs) was observed. After 24 hours, the amount of inflammatory cells had already decreased. Multiple TGF-beta 1 injections induced synovial hyperplasia and synovitis predominantly consisting of cells of the macrophage/monocyte lineage. Both single and multiple TGF-beta 1 injections induced strong and long-lasting stimulation of articular cartilage proteoglycan synthesis. This in vivo stimulation of proteoglycan synthesis was similar in cartilage of young (3 months) and old mice (18 months). Multiple TGF-beta 1 injections resulted in an increased GAG content in patellar cartilage. After triple TGF-beta 1 injections, impressive osteophyte formation was noted at specific sites. The size and the localization of osteophytes was identical in young and old mice. Interestingly, the localization of TGF-beta 1-induced osteophytes was very similar to that of osteophytes observed in experimental arthritis and osteoarthritis models, suggesting a role for endogenous TGF-beta in osteophyte formation during joint pathology.


CONCLUSIONS
Our data indicate that TGF-beta 1 injection into a normal joint induces inflammation, synovial hyperplasia, osteophyte formation, and prolonged elevation of proteoglycan synthesis and content in articular cartilage.
van Beuningen
H M
HM
Department of Rheumatology, University Hospital St. Radboud, Nijmegen, The Netherlands.
van der Kraan
P M
PM
Arntz
O J
OJ
van den Berg
W B
WB
D000818:Animals; D001345:Autoradiography; D002358:Cartilage, Articular / Q000187:drug effects* / Q000378:metabolism*; D007270:Injections, Intra-Articular; D007719:Knee Joint / Q000187:drug effects* / Q000254:growth & development* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011509:Proteoglycans / Q000096:biosynthesis*; D013583:Synovial Membrane / Q000187:drug effects / Q000473:pathology; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D011509:Proteoglycans; D016212:Transforming Growth Factor beta