Protective effects of biochanin A on articular cartilage: in vitro and in vivo studies.
BACKGROUND
Increased production of matrix metalloproteinases (MMPs) is closely related to the progression of osteoarthritis (OA). The present study was performed to investigate the potential value of biochanin A in inhibition of MMP expression in both rabbit chondrocytes and an animal model of OA.


METHODS
MTT assay was performed to assess chondrocyte survival in monolayers. The mRNA and protein expression of MMPs (including MMP-1, MMP-3, and MMP-13) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in interleukin-1 < beta > (IL-1β)-induced rabbit chondrocytes were determined by quantitative real-time PCR and enzyme-linked immunosorbent assay (ELISA), respectively. The involvement of the NF-kappaB (NF-κB) pathway activated by IL-1β was determined by western blotting. The in vivo effects of biochanin A were evaluated by intra-articular injection in an experimental OA rabbit model induced by anterior cruciate ligament transection (ACLT).


RESULTS
Biochanin A downregulated the expression of MMPs and upregulated TIMP-1 at both the mRNA and protein levels in IL-1β-induced chondrocytes in a dose-dependent manner. In addition, IL-1β-induced activation of NF-κB was attenuated by biochanin A, as determined by western blotting. Moreover, biochanin A decreased cartilage degradation as determined by both morphological and histological analyses in vivo.


CONCLUSIONS
Taken together, these findings suggest that biochanin A may be a useful agent in the treatment and prevention of OA.
Ding-Qian
DQ
Wu
Hui-ming
HM
Zhong
Qian-hai
QH
Ding
Department of Emergency Medicine, The Second Affiliated Hospital of School of Medicine, Zhejiang University, Jie Fang Road 88#, Hangzhou 310009, People's Republic of China. liba2013sky@163.com.
Li
L
Ba
D000818:Animals; D002358:Cartilage, Articular / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D002478:Cells, Cultured; D019902:Chondrocytes / Q000187:drug effects* / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D019833:Genistein / Q000494:pharmacology / Q000627:therapeutic use*; D066298:In Vitro Techniques; D007270:Injections, Intra-Articular; D053583:Interleukin-1beta / Q000378:metabolism / Q000494:pharmacology; D053509:Matrix Metalloproteinase 13 / Q000378:metabolism; D020782:Matrix Metalloproteinases / Q000235:genetics / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D010003:Osteoarthritis / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000378:metabolism; D011817:Rabbits; D060888:Real-Time Polymerase Chain Reaction; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics / Q000378:metabolism; D029921:Trifolium / Q000737:chemistry
D053583:Interleukin-1beta; D016328:NF-kappa B; D010936:Plant Extracts; D012333:RNA, Messenger; D019715:Tissue Inhibitor of Metalloproteinase-1; D019833:Genistein; D053509:Matrix Metalloproteinase 13; D020782:Matrix Metalloproteinases; C004541:biochanin A