Protective Effect Of Salidroside On Articular Cartilage In Rats With Osteoarthritis

BACKGROUND:Osteoarthritis(OA)is a common degenerative disease of joints.There is no cure for OA at present.Developing effective,reliable and safe drugs that can promote cartilage repair has been a hot and difficult issue in the treatment of OA.Rhodiola is a perennial herb of the family Sedum,which has broad-spectrum pharmacological properties.Salidroside(Sal),the main active ingredient of Rhodiola,has attracted increasing attention for its anti-injury and anti-inflammatory effects.Our and other studies have shown that salidroside has protective effects on cell damage induced by different causes,OBJECT:To investigate the protective effect of salidroside(Sal)on osteoarthritis(OA)induced by sodium monoiodoacetate(MIA)in rats and its cellular mechanism.METHODS:Male Sprague Dawley(SD)rats were divided into saline control group(NS group),monosodiun iodoacetatemodel group(MIA group)and monosodiun iodoacetate+salidroside intervention group(MIA+Sal group).MIA was injected into the knee joint cavity to establish the OA model.Sal was injected into the knee joint cavity three days after the OA model establishment,once every three days.The general conditions of rats such as spirit,activity and food intake were observed.General condition,weight,gait,joint appearance,joint diameter and weight bearing distribution of hind limbs were measured and evaluated.28 days after modeling,rats were killed by anesthesia,blood and bilateral joints were taken.Serum levels of interleukin-1 beta(IL-1?),interleukin-6(IL-6)and tumor necrosis factor-alpha(TNF-a)were measured by enzyme-linked immunosorbent assay(ELISA).The gross changes of joints were observed and scored under anatomical microscope.Histopathological changes were observed and scoredby hematoxylin-eosin(H&E)staining and safranine O-fast green staining.Rat articular chondrocytes were isolated and cultured.Live cell observation and toluidine blue staining were used to identify chondrocytes.The cells were divided into saline control group(NS group),IL-lbeta model group(IL-1[3 group)and IL-lbeta+Salidroside intervention group(IL-1??Sal group).Cell viability was measured by CCK-8,the content of prostaglandin E2(PGE2)in culture supernatant was determined by enzyme linked immunosorbent assay(ELISA),the content of nitric oxide(NO)in culture supernatant was determined by nitrate reductase method,Western Blot was used to detect the expressive levels of inducible nitric oxide synthase(iNOS),cyclooxygenase2(COX2),matrix metalloproteinase 13(MMP13),a disintegrin-like and metalloproteinase with thrombospondin motifs 5(ADAMTS5)protein,Phosphorylated nuclear factor-kappa B(pNF-kappa B)protein and total NF-kappa B protein.RESULTS:After intra-articular injection of MIA,the rats were observed the typical symptoms and signs of OA,such as joint swelling,pain behavior and movement disorder.The gross and histopathological changes of the joints showed the damage of articular cartilage.Sal intervention could significantly alleviate the general situation of OA rats,relieve joint swelling and pain behavior of OA rats,inhibit the release of IL-1?,IL-6 and TNF-a in serum of OA rats,significantly improve the degree of articular cartilage damage in OA rats,and promote the repair of articular cartilage in OA rats.At the cellular level,Sal pretreatment could inhibit the secretion of PGE2 and NO stimulated by IL-1? in isolated rat chondrocytes,reduce the expression levels of iNOS,COX2,MMP13 and ADAMTS5 proteins stimulated by IL-1? in isolated rat chondrocytes,and inhibit the activation of NF-kappa B signaling pathway.CONCLUSION:Salidroside has significant therapeutic effect on experimental OA in rats,its mechanism may be related to anti-inflammatory and chondrocyte protection,and it may become an effective therapeutic drug for osteoarthritis.