Thrombospondin 2 Promotes IL-6 Production in Osteoarthritis Synovial Fibroblasts via the PI3K/AKT/NF-κB Pathway

References

• Cho HJ, Gn KK, Kang JY, Suh KT, Kim TK. Epidemiological characteristics of patellofemoral osteoarthritis in elderly Koreans and its symptomatic contribution in knee osteoarthritis. Knee. 2016;23(1):29–34. doi:10.1016/j.knee.2015.09.003
   PubMed Web of Science ®Google Scholar
• Lawrence RC, Felson DT, Helmick CG, et al. Estimates of the prevalence of arthritis and other rheumatic conditions in the United States. Part II. Arthritis Rheum. 2008;58(1):26–35. doi:10.1002/art.23176
   PubMed Web of Science ®Google Scholar
• Dillon CF, Rasch EK, Gu Q, Hirsch R. Prevalence of knee osteoarthritis in the United States: arthritis data from the Third National Health and Nutrition Examination Survey 1991–94. J Rheumatol. 2006;33(11):2271–2279.
   PubMed Web of Science ®Google Scholar
• Loeser RF. Aging and osteoarthritis: the role of chondrocyte senescence and aging changes in the cartilage matrix. Osteoarthritis Cartilage. 2009;17(8):971–979. doi:10.1016/j.joca.2009.03.002
   PubMed Web of Science ®Google Scholar
• Krasnokutsky S, Samuels J, Abramson SB. Osteoarthritis in 2007. Bull NYU Hosp Jt Dis. 2007;65(3):222–228.
   PubMedGoogle Scholar
• Brandt KD, Dieppe P, Radin EL. Etiopathogenesis of osteoarthritis. Rheum Dis Clin North Am. 2008;34(3):531–559. doi:10.1016/j.rdc.2008.05.011
   PubMed Web of Science ®Google Scholar
• Berenbaum F. Osteoarthritis as an inflammatory disease (osteoarthritis is not osteoarthrosis!). Osteoarthr Cartil. 2013;21(1):16–21. doi:10.1016/j.joca.2012.11.012
   PubMed Web of Science ®Google Scholar
• Zhu M, Chen M, Zuscik M, et al. Inhibition of β-catenin signaling in articular chondrocytes results in articular cartilage destruction. Arthritis Rheum. 2008;58(7):2053–2064. doi:10.1002/art.23614
   PubMedGoogle Scholar
• Gu J, Rong J, Guan F, et al. Association of ADAMTS5 gene polymorphisms with osteoarthritis in Chinese Han population: a community-based case-control study. Rheumatol Int. 2013;33(11):2893–2897. doi:10.1007/s00296-012-2506-1
   PubMed Web of Science ®Google Scholar
• Glasson SS, Askew R, Sheppard B, et al. Deletion of active ADAMTS5 prevents cartilage degradation in a murine model of osteoarthritis. Nature. 2005;434(7033):644–648. doi:10.1038/nature03369
   PubMed Web of Science ®Google Scholar
• Zeng GQ, Chen AB, Li W, Song JH, Gao CY. High MMP-1, MMP-2, and MMP-9 protein levels in osteoarthritis. Genet Mol Res. 2015;14(4):14811–14822. doi:10.4238/2015.November.18.46
   PubMed Web of Science ®Google Scholar
• Saxne T, Heinegard D. Cartilage oligomeric matrix protein: a novel marker of cartilage turnover detectable in synovial fluid and blood. Br J Rheumatol. 1992;31(9):583–591. doi:10.1093/rheumatology/31.9.583
   PubMedGoogle Scholar
• Urakami T, Manki A, Inoue T, Oda M, Tanaka H, Morishima T. Clinical significance of decreased serum concentration of cartilage oligomeric matrix protein in systemic juvenile idiopathic arthritis. J Rheumatol. 2006;33(5):996–1000.
   PubMed Web of Science ®Google Scholar
• Wislowska M, Jablonska B. Serum cartilage oligomeric matrix protein (COMP) in rheumatoid arthritis and knee osteoarthritis. Clin Rheumatol. 2005;24(3):278–284. doi:10.1007/s10067-004-1000-x
   PubMed Web of Science ®Google Scholar
• Koelling S, Clauditz TS, Kaste M, Miosge N. Cartilage oligomeric matrix protein is involved in human limb development and in the pathogenesis of osteoarthritis. Arthritis Res Ther. 2006;8(3):R56. doi:10.1186/ar1922
   PubMed Web of Science ®Google Scholar
• Lohmander LS, Saxne T, Heinegard DK. Release of cartilage oligomeric matrix protein (COMP) into joint fluid after knee injury and in osteoarthritis. Ann Rheum Dis. 1994;53(1):8–13. doi:10.1136/ard.53.1.8
   PubMed Web of Science ®Google Scholar
• Pfander D, Cramer T, Deuerling D, Weseloh G, Swoboda B. Expression of thrombospondin-1 and its receptor CD36 in human osteoarthritic cartilage. Ann Rheum Dis. 2000;59(6):448–454. doi:10.1136/ard.59.6.448
   PubMed Web of Science ®Google Scholar
• Maumus M, Manferdini C, Toupet K, et al. Thrombospondin-1 partly mediates the cartilage protective effect of adipose-derived mesenchymal stem cells in osteoarthritis. Front Immunol. 2017;8:1638. doi:10.3389/fimmu.2017.01638
   PubMed Web of Science ®Google Scholar
• Maly K, Schaible I, Riegger J, Brenner RE, Meurer A, Zaucke F. The expression of thrombospondin-4 correlates with disease severity in osteoarthritic knee cartilage. Int J Mol Sci. 2019;20(2):447. doi:10.3390/ijms20020447
   PubMed Web of Science ®Google Scholar
• Calabro NE, Kristofik NJ, Kyriakides TR. Thrombospondin-2 and extracellular matrix assembly. Biochim Biophys Acta. 2014;1840(8):2396–2402. doi:10.1016/j.bbagen.2014.01.013
   PubMed Web of Science ®Google Scholar
• Helkin A, Maier KG, Gahtan V. Thrombospondin-1, −2 and −5 have differential effects on vascular smooth muscle cell physiology. Biochem Biophys Res Commun. 2015;464(4):1022–1027. doi:10.1016/j.bbrc.2015.07.044
   PubMed Web of Science ®Google Scholar
• Liu JF, Lee CW, Tsai MH, et al. Thrombospondin 2 promotes tumor metastasis by inducing matrix metalloproteinase-13 production in lung cancer cells. Biochem Pharmacol. 2018;155:537–546. doi:10.1016/j.bcp.2018.07.024
   PubMed Web of Science ®Google Scholar
• Bornstein P, Armstrong LC, Hankenson KD, Kyriakides TR, Yang Z. Thrombospondin 2, a matricellular protein with diverse functions. Matrix Biol. 2000;19(7):557–568. doi:10.1016/S0945-053X(00)00104-9
   PubMed Web of Science ®Google Scholar
• Kyriakides TR, Zhu YH, Smith LT, et al. Mice that lack thrombospondin 2 display connective tissue abnormalities that are associated with disordered collagen fibrillogenesis, an increased vascular density, and a bleeding diathesis. J Cell Biol. 1998;140(2):419–430. doi:10.1083/jcb.140.2.419
   PubMed Web of Science ®Google Scholar
• Taylor DK, Meganck JA, Terkhorn S, et al. Thrombospondin-2 influences the proportion of cartilage and bone during fracture healing. J Bone Miner Res. 2009;24(6):1043–1054. doi:10.1359/jbmr.090101
   PubMed Web of Science ®Google Scholar
• Jeong SY, Ha J, Lee M, et al. Autocrine action of thrombospondin-2 determines the chondrogenic differentiation potential and suppresses hypertrophic maturation of human umbilical cord blood-derived mesenchymal stem cells. Stem Cells. 2015;33(11):3291–3303. doi:10.1002/stem.2120
   PubMed Web of Science ®Google Scholar
• Hankenson KD, Bain SD, Kyriakides TR, Smith EA, Goldstein SA, Bornstein P. Increased marrow-derived osteoprogenitor cells and endosteal bone formation in mice lacking thrombospondin 2. J Bone Miner Res. 2000;15(5):851–862. doi:10.1359/jbmr.2000.15.5.851
   PubMed Web of Science ®Google Scholar
• Hankenson KD, Ausk BJ, Bain SD, Bornstein P, Gross TS, Srinivasan S. Mice lacking thrombospondin 2 show an atypical pattern of endocortical and periosteal bone formation in response to mechanical loading. Bone. 2006;38(3):310–316. doi:10.1016/j.bone.2005.08.027
   PubMed Web of Science ®Google Scholar
• Park YW, Kang YM, Butterfield J, Detmar M, Goronzy JJ, Weyand CM. Thrombospondin 2 functions as an endogenous regulator of angiogenesis and inflammation in rheumatoid arthritis. Am J Pathol. 2004;165(6):2087–2098. doi:10.1016/S0002-9440(10)63259-2
   PubMed Web of Science ®Google Scholar
• Tang CH, Chiu YC, Tan TW, Yang RS, Fu WM. Adiponectin enhances IL-6 production in human synovial fibroblast via an AdipoR1 receptor, AMPK, p38, and NF-κB pathway. J Immunol. 2007;179(8):5483–5492. doi:10.4049/jimmunol.179.8.5483
   PubMed Web of Science ®Google Scholar
• Chiu YC, Lin CY, Chen CP, et al. Peptidoglycan enhances IL-6 production in human synovial fibroblasts via TLR2 receptor, focal adhesion kinase, Akt, and AP-1- dependent pathway. J Immunol. 2009;183(4):2785–2792. doi:10.4049/jimmunol.0802826
   PubMed Web of Science ®Google Scholar
• Hou CH, Fong YC, Tang CH. HMGB-1 induces IL-6 production in human synovial fibroblasts through c-Src, Akt and NF-κB pathways. J Cell Physiol. 2011;226(8):2006–2015. doi:10.1002/jcp.22541
   PubMed Web of Science ®Google Scholar
• Chen HT, Tsou HK, Hsu CJ, et al. Stromal cell-derived factor-1/CXCR4 promotes IL-6 production in human synovial fibroblasts. J Cell Biochem. 2011;112(4):1219–1227. doi:10.1002/jcb.23043
   PubMed Web of Science ®Google Scholar
• Yang WH, Chang JT, Hsu SF, et al. Bradykinin enhances cell migration in human chondrosarcoma cells through BK receptor signaling pathways. J Cell Biochem. 2010;109(1):82–92.
   PubMed Web of Science ®Google Scholar
• Gerwin N, Bendele AM, Glasson S, Carlson CS. The OARSI histopathology initiative - recommendations for histological assessments of osteoarthritis in the rat. Osteoarthr Cartil. 2010;18(Suppl 3):S24–S34. doi:10.1016/j.joca.2010.05.030
   PubMed Web of Science ®Google Scholar
• Yellin MJ, Winikoff S, Fortune SM, et al. Ligation of CD40 on fibroblasts induces CD54 (ICAM-1) and CD106 (VCAM-1) up-regulation and IL-6 production and proliferation. J Leukoc Biol. 1995;58(2):209–216. doi:10.1002/jlb.58.2.209
   PubMed Web of Science ®Google Scholar
• Chen H, Sottile J, O’Rourke KM, Dixit VM, Mosher DF. Properties of recombinant mouse thrombospondin 2 expressed in Spodoptera cells. J Biol Chem. 1994;269(51):32226–32232. doi:10.1016/S0021-9258(18)31625-9
   PubMed Web of Science ®Google Scholar
• Chen PC, Tang CH, Lin LW, et al. Thrombospondin-2 promotes prostate cancer bone metastasis by the up-regulation of matrix metalloproteinase-2 through down-regulating miR-376c expression. J Hematol Oncol. 2017;10(1):33. doi:10.1186/s13045-017-0390-6
   PubMedGoogle Scholar
• Li Z, Calzada MJ, Sipes JM, et al. Interactions of thrombospondins with α4β1 integrin and CD47 differentially modulate T cell behavior. J Cell Biol. 2002;157(3):509–519. doi:10.1083/jcb.200109098
   PubMed Web of Science ®Google Scholar
• Bancroft T, Bouaouina M, Roberts S, et al. Up-regulation of thrombospondin-2 in Akt1-null mice contributes to compromised tissue repair due to abnormalities in fibroblast function. J Biol Chem. 2015;290(1):409–422. doi:10.1074/jbc.M114.618421
   PubMed Web of Science ®Google Scholar
• Chen H, Strickland DK, Mosher DF. Metabolism of thrombospondin 2. Binding and degradation by 3t3 cells and glycosaminoglycan-variant Chinese hamster ovary cells. J Biol Chem. 1996;271(27):15993–15999. doi:10.1074/jbc.271.27.15993
   PubMed Web of Science ®Google Scholar
• Urtasun R, Lopategi A, George J, et al. Osteopontin, an oxidant stress sensitive cytokine, up-regulates collagen-I via integrin αVβ3 engagement and PI3K/pAkt/NFκB signaling. Hepatology. 2012;55(2):594–608. doi:10.1002/hep.24701
   PubMed Web of Science ®Google Scholar
• Shao G, Liu Y, Ma T, Zhang L, Yuan M, Zhao S. GCN5 inhibition prevents IL-6-induced prostate cancer metastases through PI3K/PTEN/Akt signaling by inactivating Egr-1. Biosci Rep. 2018;38(6). doi:10.1042/BSR20180816
   Google Scholar
• Zhou J, Sun X, Zhang J, Yang Y, Chen D, Cao J. IL-34 regulates IL-6 and IL-8 production in human lung fibroblasts via MAPK, PI3K-Akt, JAK and NF-κB signaling pathways. Int Immunopharmacol. 2018;61:119–125. doi:10.1016/j.intimp.2018.05.023
   PubMed Web of Science ®Google Scholar
• Wei L, Xiong H, Li W, Li B, Cheng Y. Upregulation of IL-6 expression in human salivary gland cell line by IL-17 via activation of p38 MAPK, ERK, PI3K/Akt, and NF-kappaB pathways. J Oral Pathol Med. 2018;47(9):847–855. doi:10.1111/jop.12765
   PubMed Web of Science ®Google Scholar
• Hayami T, Pickarski M, Zhuo Y, Wesolowski GA, Rodan GA, Duong LT. Characterization of articular cartilage and subchondral bone changes in the rat anterior cruciate ligament transection and meniscectomized models of osteoarthritis. Bone. 2006;38(2):234–243. doi:10.1016/j.bone.2005.08.007
   PubMed Web of Science ®Google Scholar
• Lee CH, Seto WK, Lui DT, et al. Circulating thrombospondin-2 as a novel fibrosis biomarker of nonalcoholic fatty liver disease in type 2 diabetes. Diabetes Care. 2021;44(9):2089–2097. doi:10.2337/dc21-0131
   PubMed Web of Science ®Google Scholar
• Kozumi K, Kodama T, Murai H, et al. Transcriptomics identify thrombospondin-2 as a biomarker for NASH and advanced liver fibrosis. Hepatology. 2021. doi:10.1002/hep.31995
   PubMed Web of Science ®Google Scholar
• Kimura T, Tanaka N, Fujimori N, et al. Serum thrombospondin 2 is a novel predictor for the severity in the patients with NAFLD. Liver Int. 2021;41(3):505–514. doi:10.1111/liv.14776
   PubMed Web of Science ®Google Scholar
• Deng LY, Zeng XF, Tang D, Deng W, Liu HF, Xie YK. Expression and prognostic significance of thrombospondin gene family in gastric cancer. J Gastrointest Oncol. 2021;12(2):355–364. doi:10.21037/jgo-21-54
   PubMed Web of Science ®Google Scholar
• Peng HY, Chang MC, Hu CM, Yang HI, Lee WH, Chang YT. Thrombospondin-2 is a highly specific diagnostic marker and is associated with prognosis in pancreatic cancer. Ann Surg Oncol. 2019;26(3):807–814. doi:10.1245/s10434-018-07109-6
   PubMed Web of Science ®Google Scholar
• Jiang YM, Yu DL, Hou GX, Jiang JL, Zhou Q, Xu XF. Serum thrombospondin-2 is a candidate diagnosis biomarker for early non-small-cell lung cancer. Biosci Rep. 2019;39(7). doi:10.1042/BSR20190476
   Google Scholar
• Wang X, Zhang L, Li H, Sun W, Zhang H, Lai M. THBS2 is a potential prognostic biomarker in colorectal cancer. Sci Rep. 2016;6:33366. doi:10.1038/srep33366
   PubMed Web of Science ®Google Scholar
• MacLauchlan S, Yu J, Parrish M, et al. Endothelial nitric oxide synthase controls the expression of the angiogenesis inhibitor thrombospondin 2. Proc Natl Acad Sci U S A. 2011;108(46):E1137–E1145. doi:10.1073/pnas.1104357108
   PubMed Web of Science ®Google Scholar
• Roudnicky F, Yoon SY, Poghosyan S, et al. Alternative transcription of a shorter, non-anti-angiogenic thrombospondin-2 variant in cancer-associated blood vessels. Oncogene. 2018;37(19):2573–2585. doi:10.1038/s41388-018-0129-z
   PubMed Web of Science ®Google Scholar
• Lamy L, Foussat A, Brown EJ, Bornstein P, Ticchioni M, Bernard A. Interactions between CD47 and thrombospondin reduce inflammation. J Immunol. 2007;178(9):5930–5939. doi:10.4049/jimmunol.178.9.5930
   PubMed Web of Science ®Google Scholar
• Daniel C, Wagner A, Hohenstein B, Hugo C. Thrombospondin-2 therapy ameliorates experimental glomerulonephritis via inhibition of cell proliferation, inflammation, and TGF-β activation. Am J Physiol Renal Physiol. 2009;297(5):F1299–F1309. doi:10.1152/ajprenal.00254.2009
   PubMed Web of Science ®Google Scholar
• Maly K, Andres Sastre E, Farrell E, Meurer A, Zaucke F. COMP and TSP-4: functional roles in articular cartilage and relevance in osteoarthritis. Int J Mol Sci. 2021;22(5):2242. doi:10.3390/ijms22052242
   PubMed Web of Science ®Google Scholar
• Tseng S, Reddi AH, Di Cesare PE. Cartilage oligomeric matrix protein (COMP): a biomarker of arthritis. Biomark Insights. 2009;4:33–44. doi:10.4137/BMI.S645
   PubMedGoogle Scholar
• Chen FH, Thomas AO, Hecht JT, Goldring MB, Lawler J. Cartilage oligomeric matrix protein/thrombospondin 5 supports chondrocyte attachment through interaction with integrins. J Biol Chem. 2005;280(38):32655–32661. doi:10.1074/jbc.M504778200
   PubMed Web of Science ®Google Scholar
• Goldring MB, Goldring SR. Osteoarthritis. J Cell Physiol. 2007;213(3):626–634. doi:10.1002/jcp.21258
   PubMed Web of Science ®Google Scholar
• Zheng W, Feng Z, You S, et al. Fisetin inhibits IL-1β-induced inflammatory response in human osteoarthritis chondrocytes through activating SIRT1 and attenuates the progression of osteoarthritis in mice. Int Immunopharmacol. 2017;45:135–147. doi:10.1016/j.intimp.2017.02.009
   PubMed Web of Science ®Google Scholar
• Wu X, Cao L, Li F, Ma C, Liu G, Wang Q. Interleukin-6 from subchondral bone mesenchymal stem cells contributes to the pathological phenotypes of experimental osteoarthritis. Am J Transl Res. 2018;10(4):1143–1154.
   PubMed Web of Science ®Google Scholar
• Husby G, Williams RC. Synovial localization of tumor necrosis factor in patients with rheumatoid arthritis. J Autoimmun. 1988;1(4):363–371. doi:10.1016/0896-8411(88)90006-6
   PubMed Web of Science ®Google Scholar
• Mattila P, Majuri ML, Mattila PS, Renkonen R. TNF alpha-induced expression of endothelial adhesion molecules, ICAM-1 and VCAM-1, is linked to protein kinase C activation. Scand J Immunol. 1992;36(2):159–165. doi:10.1111/j.1365-3083.1992.tb03087.x
   PubMed Web of Science ®Google Scholar
• Martini M, De Santis MC, Braccini L, Gulluni F, Hirsch E. PI3K/AKT signaling pathway and cancer: an updated review. Ann Med. 2014;46(6):372–383. doi:10.3109/07853890.2014.912836
   PubMed Web of Science ®Google Scholar
• Ao R, Guan L, Wang Y, Wang JN. Silencing of COL1A2, COL6A3, and THBS2 inhibits gastric cancer cell proliferation, migration, and invasion while promoting apoptosis through the PI3k-Akt signaling pathway. J Cell Biochem. 2018;119(6):4420–4434. doi:10.1002/jcb.26524
   PubMed Web of Science ®Google Scholar
• Sun HZ, Yang TW, Zang WJ, Wu SF. Dehydroepiandrosterone-induced proliferation of prostatic epithelial cell is mediated by NFKB via PI3K/AKT signaling pathway. J Endocrinol. 2010;204(3):311–318. doi:10.1677/JOE-09-0270
   PubMed Web of Science ®Google Scholar
• Zhang XY, Liu Y, He T, et al. Anaphylatoxin C5a induces inflammation and reduces insulin sensitivity by activating TLR4/NF-kB/PI3K signaling pathway in 3T3-L1 adipocytes. Biomed Pharmacother. 2018;103:955–964. doi:10.1016/j.biopha.2018.04.057
   PubMed Web of Science ®Google Scholar