Proteoglycan loss and subsequent replenishment in articular cartilage after a mild arthritic insult by IL-1 in mice: impaired proteoglycan turnover in the recovery phase.
The reparative responses of articular cartilage after an arthritic insult have not been studied extensively to this day. In the present study, we injected interleukin-1 (IL-1) into knee joints of mice to provoke a mild and transient arthritic insult, and characterized both the catabolic and the subsequent recovery phase. In the catabolic phase, which lasted 2 days after IL-1 injection, proteoglycan (PG) breakdown was profoundly accelerated and PG synthesis was markedly inhibited. Sulfation and polysaccharide synthesis were not affected, yet the number of chondroitin sulfate chains was decreased. The general chondrocyte protein synthesis was not inhibited by IL-1. IL-1 injected every other day for a total of three injections prolonged this catabolic phase and resulted in frank loss of articular cartilage proteoglycans. In the recovery phase, started 3 days after IL-1, PG synthesis was enhanced (1.7 times the normal) and proteoglycans had normal hydrodynamic properties. Remarkably, PG degradation was significantly decreased (approximately 50% of the normal). Zymographic analysis demonstrated enhanced expression of gelatinolytic activities in the extracts of the articular tissues shortly after IL-1 exposure and decreased levels in the recovery phase. We found that the overshoot of PG synthesis and impaired degradation act together to facilitate full cartilage repair 7 days after the last of the three IL-1 injections.
van de Loo
A A
AA
Department of Rheumatology, University Hospital Nijmegen, The Netherlands.
Arntz
O J
OJ
Otterness
I G
IG
van den Berg
W B
WB
D000818:Animals; D002358:Cartilage, Articular / Q000166:cytology / Q000187:drug effects* / Q000473:pathology; D002460:Cell Line; D004195:Disease Models, Animal; D004591:Electrophoresis, Polyacrylamide Gel; D018093:Gelatinases / Q000096:biosynthesis; D006820:Hyaluronic Acid / Q000378:metabolism*; D007375:Interleukin-1 / Q000008:administration & dosage / Q000633:toxicity*; D007719:Knee Joint / Q000187:drug effects; D008297:Male; D008666:Metalloendopeptidases / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D010003:Osteoarthritis / Q000139:chemically induced* / Q000378:metabolism; D011134:Polysaccharides / Q000096:biosynthesis; D011509:Proteoglycans / Q000378:metabolism*
D007375:Interleukin-1; D011134:Polysaccharides; D011509:Proteoglycans; D006820:Hyaluronic Acid; D018093:Gelatinases; D008666:Metalloendopeptidases