Effect of dehydroepiandrosterone on cartilage and synovium of knee joints with osteoarthritis in rabbits.
The aim of this study was to investigate the effects of intra-articular injection of dehydroepiandrosterone (DHEA) on cartilage and synovium of knee joints with osteoarthritis (OA) in rabbits and the underlying mechanism. Forty rabbits underwent unilateral anterior cruciate ligament transaction and were divided into two groups. Rabbits were injected with 100 mumol/l DHEA dissolved in the dimethylsulphoxide (DMSO) in the knee joints 5 weeks after transaction, once a week for 5 weeks. Rabbits injected with DMSO under the same condition were served as a control. All rabbits were killed 1 week after the last injection. The knee joints were evaluated by gross morphology, histology, and gene expression analysis. Gross morphologic inspection and histological evaluation showed that the DHEA group appeared less damage in cartilage and synovium as compared with the control. Gene expression analysis revealed that the mRNA expression of matrix metalloproteinase-3 (MMP-3) in cartilage and synovium decreased significantly in the DHEA group and that of tissue inhibitor of metalloproteinase-1 (TIMP-1) increased. No significant difference of interleukin-1 beta (IL-1beta) mRNA expression was found in the cartilage between two groups while the mRNA expression of IL-1beta in the synovium was largely suppressed in the DHEA group. The study suggests that DHEA plays a protective role against cartilage degradation and synovium inflammation in rabbits with OA. This role may be achieved through the regulation of the MMP-3, TIMP-1, and IL-1beta gene expression in the cartilage and synovium.
Wu
Li Dong
LD
Department of Orthopaedics, The 2nd Hospital of Medical College, Zhejiang University, Hangzhou, People's Republic of China. ldwu@yahoo.com
Yu
Hua Chen
HC
Xiong
Yan
Y
Feng
Jie
J
D000818:Animals; D016118:Anterior Cruciate Ligament / Q000601:surgery; D002356:Cartilage / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D003687:Dehydroepiandrosterone / Q000008:administration & dosage / Q000494:pharmacology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D007270:Injections, Intra-Articular; D053583:Interleukin-1beta / Q000378:metabolism; D007719:Knee Joint / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D019278:Matrix Metalloproteinase 3 / Q000378:metabolism; D010003:Osteoarthritis / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D011817:Rabbits; D013583:Synovial Membrane / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism
D053583:Interleukin-1beta; D012333:RNA, Messenger; D019715:Tissue Inhibitor of Metalloproteinase-1; D003687:Dehydroepiandrosterone; D019278:Matrix Metalloproteinase 3