Effects of sodium ferulate on human osteoarthritic chondrocytes and osteoarthritis in rats.
1. Oxidation, inflammation and apoptosis are involved in the aetiology and pathology of osteoarthritis (OA). Sodium ferulate (SF) has been demonstrated to have anti-oxidant, anti-inflammatory and anti-apoptotic actions in cardiovascular, hepatic and diabetic disorders. These findings suggest that SF may have beneficial effects on OA. Therefore, present study investigated the effects of SF in an in vivo rat OA model, as well as in vitro in human OA chondrocytes. 2. Rats were divided into the following groups: (i) an untreated control group; (ii) papain-induced OA; (iii) OA rats treated with 0.1 or 0.5% SF; and (iv) normal rats injected with 0.5% SF intra-articularly. Human chondrocytes from OA patients were cultured before being stimulated with 2 ng/mL interleukin-1β and subsequently treated with SF (125, 250 and 500 μmol/L). The effects of SF were evaluated both in vivo and in vitro. 3. In OA rats, SF treatment dose-dependently reversed pathological changes in OA cartilage, decreased BAX-immunopositive chondrocytes and increased Bcl-2-immunopositive chondrocytes. Both in vivo and in vitro analyses demonstrated a significant decrease in matrix metalloproteinase-1 and an increase in tissue-specific inhibitor of metalloproteinase-1. In vitro, SF enhanced chondrocyte proliferation and decreased nitric oxide production and apoptosis. 4. The results demonstrate that SF dose-dependently suppresses pathological processes in both in vitro and in vivo OA models. Thus, SF could be a therapeutic strategy for the treatment of OA.
Shang
Liang
L
Department of Orthopaedic Surgery, Zhongnan Hospital, Wuhan University, Wuhan, China.
Qin
Jun
J
Chen
Liao-Bin
LB
Liu
Bao-Xin
BX
Jacques
Magdalou
M
Wang
Hui
H
D000368:Aged; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D019902:Chondrocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D003373:Coumaric Acids / Q000494:pharmacology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007150:Immunohistochemistry; D053583:Interleukin-1beta / Q000378:metabolism; D007719:Knee Joint / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism; D008875:Middle Aged; D009569:Nitric Oxide / Q000378:metabolism; D020370:Osteoarthritis, Knee / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D010206:Papain; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
C494828:Bax protein, rat; D003373:Coumaric Acids; D053583:Interleukin-1beta; D019253:Proto-Oncogene Proteins c-bcl-2; C560822:TIMP1 protein, human; C576839:TIMP1 protein, rat; D019715:Tissue Inhibitor of Metalloproteinase-1; D051028:bcl-2-Associated X Protein; D009569:Nitric Oxide; C004999:ferulic acid; D010206:Papain; C522360:MMP1 protein, human; C576840:MMP1 protein, rat; D020781:Matrix Metalloproteinase 1