RESUMO
BACKGROUND: Icariin (ICA) is an active compound extracted from Epimedium brevicornum Maxim. Previous reports have shown that icariin has a clinically significant therapeutic effect on rheumatoid arthritis. However, little is known about the mechanism by which icariin inhibits cartilage and bone degradation. METHODS: New Zealand rabbits were immunized with antigen-induced arthritis (AIA) and treated with icariin. Joint tissues from rabbits were studied by histological analysis, transmission electron microscopy (TEM), and micro-CT. The expression levels of receptor activator of nuclear factor-B ligand (RANKL) and osteoprotegerin (OPG) in joint tissues were determined using immunohistochemistry and real-time PCR analysis. RESULTS: Histological analysis and TEM sections of cartilage in the ICA treated group showed a low level of chondrocyte destruction. Micro-CT analysis showed that the bone mineral density value and bone structural level in ICA treated rabbits were significantly higher compared with those in the AIA group. Immunohistochemistry and real-time PCR analysis showed that icariin treatment reduced RANKL expression and enhanced OPG expression levels, as compared to the AIA group. CONCLUSION: These data indicate that ICA suppresses articular bone loss and prevents joint destruction. This study also determined that ICA regulated articular bone loss in part by regulating RANKL and OPG expression.
Assuntos
Artrite Experimental/tratamento farmacológico , Doenças Ósseas/tratamento farmacológico , Cartilagem/patologia , Flavonoides/uso terapêutico , Animais , Cartilagem/efeitos dos fármacos , Cartilagem/ultraestrutura , Microscopia Eletrônica de Transmissão , Modelos Teóricos , Osteoprotegerina/metabolismo , Ligante RANK/metabolismo , CoelhosRESUMO
BACKGROUND: Total glucosides of paeony (TGP) is a biologically active compound extracted from Paeony root. TGP has been used in rheumatoid arthritis therapy for many years. However, the mechanism by which TGP prevents bone loss has been less explored. METHODS: TGP was orally administered for 3 months to New Zealand rabbits with antigen-induced arthritis (AIA). Digital x-ray knee images and bone mineral density (BMD) measurements of the subchondral knee bone were performed before sacrifice. Chondrocytes were observed using transmission electron microscopy (TEM). Histological analysis and mRNA expression of receptor activator of nuclear factor-B ligand (RANKL) and osteoprotegerin (OPG) were evaluated in joint tissues. RESULTS: The BMD value in TGP rabbits was significantly higher compared with that seen in the AIA model rabbits. In addition, the subchondral bone plate was almost completely preserved by TGP treatment, while there was a decrease in bone plate integrity in AIA rabbits. There was less damage to the chondrocytes of the TGP treated group. Immunohistochemical examination of the TGP group showed that a higher percentage of TGP treated chondrocytes expressed OPG as compared to the chondrocytes isolated from AIA treated animals. In contrast, RANKL expression was significantly decreased in the TGP treated group compared to the AIA group. In support of the immunohistochemistry data, the expression of RANKL mRNA was decreased and OPG mRNA expression was enhanced in the TGP group when compared to that of the AIA model group. CONCLUSION: These results reveal that TGP suppresses juxta-articular osteoporosis and prevents subchondral bone loss. The decreased RANKL and increased OPG expression seen in TGP treated animals could explain how administration of TGP maintains higher BMD.
Assuntos
Artrite Experimental/complicações , Artrite Reumatoide/complicações , Reabsorção Óssea/prevenção & controle , Glucosídeos/uso terapêutico , Osteoporose/prevenção & controle , Paeonia/química , Fitoterapia , Animais , Artrite Experimental/tratamento farmacológico , Artrite Experimental/metabolismo , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/metabolismo , Densidade Óssea , Reabsorção Óssea/metabolismo , Condrócitos/metabolismo , Glucosídeos/farmacologia , Articulação do Joelho/metabolismo , Osteoporose/metabolismo , Osteoprotegerina/genética , Osteoprotegerina/metabolismo , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Raízes de Plantas , Ligante RANK/genética , Ligante RANK/metabolismo , RNA Mensageiro/metabolismo , CoelhosRESUMO
Although a number of anti-rheumatic drugs and biologics may be used to alleviate the symptoms of rheumatoid arthritis (RA), these compounds have been associated with bone loss and joint destruction; thus, alternative treatment approaches are required. In the present study, various plant extracts were evaluated for their capacity to inhibit joint destruction, and Panax notoginseng saponins (PNS), obtained from the Traditional Chinese Medicine Panax notoginseng, was identified as such a compound. Therefore, a rabbit antigen-induced arthritis (AIA) model was generated by immunization with ovalbumin in Freund's complete adjuvant, followed by treatment with PNS for 3 months. The morphology of the quadriceps femoris muscle, cartilage chondrocytes and skeletal elements was histologically observed by transmission electron microscopy (TEM), as well as micro-computed tomography. The results revealed that PNS significantly reduced the histopathological alterations associated with arthritic muscular atrophy and inflammation. In addition, TEM demonstrated that PNS protected chondrocytes from RA-associated damage. Furthermore, the bone density and microarchitecture in rabbits treated with PNS were markedly improved compared with those of the model group. Collectively, these data indicated that treatment with PNS may relieve osteoporosis and prevent joint and bone destruction in AIA.