Anti-arthritic effects of crocin in interleukin-1β-treated articular chondrocytes and cartilage in a rabbit osteoarthritic model.
OBJECTIVE
Interleukin-1β-mediated production of matrix metalloproteinases (MMPs) plays a pivotal role in the process of osteoarthritis. Crocin, a pharmacologically active component of Crocus sativus L. (saffron), has been used in Chinese traditional medicine. In this study, we aimed to investigate the effects of crocin on MMP-1, MMP-3 and MMP-13 expression in rabbit chondrocytes induced by interleukin-1β (IL-1β) and in an experimental rabbit model induced by anterior cruciate ligament transection.


METHODS
Chondrocytes isolated from the articular cartilage of 4-week-old rabbits were cultured and passaged. Confluent chondrocytes were treated with various concentrations of crocin in the presence or absence of IL-1β (10 ng/ml) for 24 h. Quantitative real-time polymerase chain reaction, enzyme-linked immunosorbent assay, and Western blotting were used to investigate the expression of inducible MMP-1, MMP-3 and MMP-13. In addition, the in-vivo effects of crocin were assessed by morphological and histological analysis.


RESULTS
IL-1β markedly upregulated the expression of MMP-1, -3 and -13 in chondrocytes, and this activation was inhibited by co-incubation with crocin in a dose-dependent manner, in contrast with the control group. Moreover, crocin inhibited IL-1β-induced activation of the nuclear factor kappa B pathway through suppressing degradation of inhibitory-kappa-B-α. In-vivo investigations showed that crocin ameliorated cartilage degeneration and that expression of the MMP-1, -3 and -13 genes in cartilage was significantly inhibited by crocin.


CONCLUSIONS
Taken together, our findings suggest that the anti-inflammatory activity of crocin may be of potential value in the prevention and treatment of osteoarthritis.
Department of Orthopedic Surgery, The Second Affiliated Hospital of School of Medicine, Zhejiang University, Jie Fang Road 88#, Hangzhou, People's Republic of China.
Qianhai
Q
Ding
Huiming
H
Zhong
Yiying
Y
Qi
Ye
Y
Cheng
Weijun
W
Li
Shigui
S
Yan
Xianghua
X
Wang
D000818:Animals; D002338:Carotenoids / Q000494:pharmacology* / Q000627:therapeutic use; D002358:Cartilage, Articular / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D019902:Chondrocytes / Q000187:drug effects*; D005260:Female; D053583:Interleukin-1beta / Q000494:pharmacology*; D020782:Matrix Metalloproteinases / Q000096:biosynthesis; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D010003:Osteoarthritis / Q000188:drug therapy*; D011817:Rabbits
D053583:Interleukin-1beta; D016328:NF-kappa B; D002338:Carotenoids; C029036:crocin; D020782:Matrix Metalloproteinases