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Journal of ZheJiang University(Medical Science)  2016, Vol. 45 Issue (5): 453-460    DOI: 10.3785/j.issn.1008-9292.2016.09.02
Protective effect of diosgenin on chondrocytes mediated by JAK2/STAT3 signaling pathway in mice with osteoarthritis
LIU Jun1, HE Xiaole2, ZHEN Ping1, ZHOU Shenghu1, LI Xusheng1
1. Department of Orthopaedics Center, Lanzhou General Hospital of PLA, Lanzhou 730050, China;
2. Department of Gerontology, Xijing Hospital, the Fourth Military Medical University, Xi'an 710032, China
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Objective: To investigate the effect of diosgenin (Dgn) on chondrocytes and its relation to JAK2/STAT3 signaling pathway in mice with osteoarthritis (OA).Methods: Fifteen male C57BL/6 mice were randomly divided into three groups:control group, OA group and OA+Dgn group. After 4 weeks of treatment, the histopathological changes of cartilage tissue were observed by toluidine blue staining under light microscopy and the ultrastructure of chondrocytes was observed under electron microscopy. The primarily cultured chondrocytes of OA mice were randomly divided into 4 groups:(1) OA group, (2) Dgn group, (3) Dgn+AG490 group, (4) AG490 group. The expression of p-JAK2, p-STAT3, Bax, succinate dehydrogenase (SDH) and cytochrome c oxidase (COX) were detected by Western blotting, and superoxide dismutase (SOD) was detected using colorimetric method. Results: The morphological observation showed that the chondrocytes of OA group presented considerable pathological changes, while the chondrocytes in OA+Dgn group maintained intact membrane. Electron microscopy observation found obvious injury in cartilage tissues of OA group, while that in OA+Dgn group remained smooth. Compared with OA group, the expressions of p-JAK2 and p-STAT3 in chondrocytes of Dgn group were increased (all P<0.05), and the expressions of Bax protein, SDH, COX and SOD were decreased (all P<0.05). While compared with Dgn group, the expressions of p-JAK2, p-STAT3, SDH, COX and SOD in chondrocytes of Dgn+AG490 group were decreased (all P<0.05), and the expression of Bax protein was increased (P<0.05). Conclusion: Diosgenin can inhibit apoptosis and increase mitochondrial oxidative stress capacity of chondrocytes in mice with osteoarthritis, which is closely related to the activation of JAK2/STAT3 signaling pathway.

Key wordsOsteoarthritis/pathology      Dioscin/pharmacology      STAT3 transcription factor      Protein-tyrosine kinases      Chondrocytes/pathology      Oxidative stress     
Received: 08 January 2016      Published: 25 September 2016
CLC:  R684  
Cite this article:

LIU Jun, HE Xiaole, ZHEN Ping, ZHOU Shenghu, LI Xusheng. Protective effect of diosgenin on chondrocytes mediated by JAK2/STAT3 signaling pathway in mice with osteoarthritis. Journal of ZheJiang University(Medical Science), 2016, 45(5): 453-460.

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关键词: 骨关节炎/病理学,  薯蓣皂甙/药理学,  STAT3转录因子,  蛋白酪氨酸激酶类,  软骨细胞/病理学,  氧化性应激 
[[1]]   KRAUS V B, KILFOIL T M, HASH T W, et al.Atlas of radiographic features of osteoarthritis of the ankle and hindfo[J].Osteoarthritis Cartilage, 2015, 23(12):2059-2085.
[[2]]   付博, 杨宝林.骨性关节炎研究进展[J].辽宁中医药大学学报, 2014, 16(7):243-246.FU Bo, YANG Baolin.Study progress of osteoarthritis[J].Journal of Liaoning University of TCM, 2014, 16(7):243-246.(in Chinese)
[[3]]   张荣凯, 杨禄坤, 黄丽娟, 等.脂蛋白基因在早期骨关节炎软骨下骨的表达[J].中国骨伤, 2014, 27(1):54-57.ZHANG Rongkai, YANG Lukun, HUANG Lijuan, et al.Expression of lipoprotein related genes in subchondral bone of early experimental osteoarthritis[J].China Journal of Orthopaedics and Traumatology, 2014, 27(1):54-57.(in Chinese)
[[4]]   WHITWORTH D J, BANKS T A.Stem cell therapies for treating osteoarthritis:prescient or premature[J].Vet J, 2014, 202(3):416-424.
[[5]]   KLAG K A, HORTON W A.Advances in treatment of achondroplasia and osteoarthritis[J].Hum Mol Genet, 2016, 25(R1):R2-R8.
[[6]]   LEPAGE C, LÉGER D Y, BERTRAND J, et al.Diosgenin induces death receptor-5 through activation of p38 pathway and promotes TRAIL-induced apoptosis in colon cancer cells[J].Cancer Lett, 2011, 301(2):193-202.
[[7]]   SHISHODIA S, AGGARWAL B.Diosgenin inhibits osteoclastogenesis, invasion, and proliferation through the downregulation of Akt, IκB kinase activation and NF-κB-regulated gene expression[J].Oncogene, 2006, 25(10):1463-1473.
[[8]]   SAHA S, GOSWAMI G, PANDRANGI A.Isolation and prevention of calcium oxalate-induced apoptotic death and oxidative stress in MDCK cells by diosgenin[J].Chem Biol Interact, 2014, 224C:51-57.
[[9]]   CHEN P S, SHIH Y H, HUANG H C, et al.Diosgenin, a steroidal saponin, inhibits migration and invasion of human prostate cancer PC-3 cells by reducing matrix metalloproteinases expression[J/OL].PLoS One, 2011, 6(5):e20164.
[[10]]   LI C H, XU L L, ZHAO J X, et al.CXCL16 upregulates RANKL expression in rheumatoid arthritis synovial fibroblasts through the JAK2/STAT3 and p38/MAPK signaling pathway[J].Inflamm Res, 2016, 65(3):193-202.
[[11]]   OHBA S, LANIGAN T M, ROESSLER B J.Leptin receptor JAK2/STAT3 signaling modulates expression of Frizzled receptors in articular chondrocytes[J].Osteoarthritis Cartilage, 2010, 18(12):1620-1629.
[[12]]   DE ANDRÉS M C, IMAGAWA K, HASHIMOTO K, et al.Suppressors of cytokine signalling (SOCS) are reduced in osteoarthritis[J].Biochem Biophys Res Commun, 2011, 407(1):54-59.
[[13]]   任红革, 崔逢德.细胞因子在骨性关节炎中的表达与应用[J].中国组织工程研究, 2012, 16(52):9828-9835.REN Hongge, CUI Fengde.Expression and application of cytokines in osteoarthritis[J].Chinese Journal of Tissue Engineering Research, 2012, 16(52):9828-9835.(in Chinese)
[[14]]   JUNG D H, PARK H J, BYUN H E, et al.Diosgenin inhibits macrophage-derived inflammatory mediators through downregulation of CK2, JNK, NF-κB and AP-1 activation[J].Int Immunopharmacol, 2010, 10(9):1047-1054.
[[15]]   WANG L, MA T, ZHENG Y, et al.Diosgenin inhibits IL-1β-induced expression of inflammatory mediators in human osteoarthritis chondrocytes[J].Int J Clin Exp Pathol, 2015, 8(5):4830-4836.
[[16]]   TERRELL A M, CRISOSTOMO P R, WAIRIUKO G M, et al.Jak/STAT/SOCS signaling circuits and associated cytokine-mediated inflammation and hypertrophy in the heart[J].Shock, 2006, 26(3):226-234.
[[17]]   PARK S K, DAHMER M K, QUASNEY M W.MAPK and JAK-STAT signaling pathways are involved in the oxidative stress-induced decrease in expression of surfactant protein genes[J].Cell Physiol Biochem, 2012, 30(2):334-346.
[[18]]   WEN S H, LI Y, LI C, et al.Ischemic postconditioning during reperfusion attenuates intestinal injury and mucosal cell apoptosis by inhibiting JAK/STAT signaling activation[J].Shock, 2012, 38(4):411-419.
[[19]]   YAMMANI R R, LONG D, LOESER R F.Interleukin-7 stimulates secretion of S100A4 by activating the JAK/STAT signaling pathway in human articular chondrocytes[J].Arthritis Rheum, 2009, 60(3):792-800.
[[20]]   MILLWARD-SADLER S J, KHAN N S, BRACHER M G, et al.Roles for the interleukin-4 receptor and associated JAK/STAT proteins in human articular chondrocyte mechanotransduction[J].Osteoarthritis Cartilage, 2006, 14(10):991-1001.
[[21]]   TEIXEIRA C C, LIU Y, THANT L M, et al.Foxo1, a novel regulator of osteoblast differentiation and skeletogenesis[J].J Biol Chem, 2010, 285(40):31055-31065.
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