Anti-arthritic effects of chlorogenic acid in interleukin-1β-induced rabbit chondrocytes and a rabbit osteoarthritis model.
Cartilage degradation is one of the pathological changes of osteoarthritis (OA), and accumulating evidence suggests an excess of matrix metalloproteinases (MMPs) plays a role in this cartilage breakdown. Here, we investigated the effects of chlorogenic acid (CGA) on the mRNA and protein expression of MMPs in interleukin (IL)-1β-induced rabbit chondrocytes and evaluated the in vivo effects of CGA in experimental OA induced by anterior cruciate ligament transection (ACLT) in rabbits. Using quantitative real-time PCR and ELISA to investigate the expression levels of MMP-1, MMP-3, MMP-13, and tissue inhibitors of metalloproteinase-1(TIMP-1) in IL-1β-induced rabbit chondrocytes, we showed that CGA inhibits the expression of these MMPs while increasing TIMP-1 expression, at both the mRNA and protein levels. In addition, IL-1β-induced activation of nuclear factor kappa B (NF-κB) and the degradation of inhibitor of κB (IκB)-α were suppressed by CGA. In rabbits, CGA decreased cartilage degradation as assessed by morphological and histological analyses. The down-regulation of MMP-1, MMP-3, and MMP-13 expression and up-regulation of TIMP-1 expression were also detected in CGA-treated cartilage compared with vehicle-treated cartilage, confirming these findings in an in vivo model. Taken together, these findings indicate that CGA may be considered as a possible candidate agent in the treatment of OA.
Chen
Wei-Ping
WP
Department of Orthopedics Surgery, The Second Affiliated Hospital of Medical College, Zhejiang University, China.
Tang
Jing-Li
JL
Bao
Jia-Peng
JP
Hu
Peng-Fei
PF
Shi
Zhong-Li
ZL
Wu
Li-Dong
LD
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000627:therapeutic use*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002726:Chlorogenic Acid / Q000008:administration & dosage / Q000627:therapeutic use*; D019902:Chondrocytes / Q000276:immunology*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D053583:Interleukin-1beta / Q000276:immunology*; D020782:Matrix Metalloproteinases / Q000096:biosynthesis* / Q000235:genetics; D016328:NF-kappa B / Q000276:immunology; D010003:Osteoarthritis / Q000188:drug therapy* / Q000276:immunology; D011817:Rabbits; D011994:Recombinant Proteins / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000894:Anti-Inflammatory Agents, Non-Steroidal; D053583:Interleukin-1beta; D016328:NF-kappa B; D011994:Recombinant Proteins; D002726:Chlorogenic Acid; D020782:Matrix Metalloproteinases