山东大学学报 (医学版) ›› 2019, Vol. 57 ›› Issue (5): 80-86.doi: 10.6040/j.issn.1671-7554.0.2019.021
• • 上一篇
陈虹瑜1,2,曲竹丽3,孙琪4,赵华强1,5,马川1,5
CHEN Hongyu1,2,QU Zhuli3, SUN Qi4, ZHAO Huaqiang1,5, MA Chuan1,5
摘要: 目的 探讨白介素-1β(IL-1β)介导下细胞外调节蛋白激酶(ERK)通路对大鼠髁突软骨细胞外基质的作用。 方法 对Wistar大鼠髁突软骨细胞进行培养和鉴定。采用不同浓度的IL-1β处理髁突软骨细胞,检测ERK、Sry相关高速泳动族框因子9(Sox-9)、Ⅱ型胶原(COL2)的 mRNA表达,检测ERK、磷酸化ERK(P-ERK)、Sox-9、COL2的蛋白表达,并由此确定诱导细胞致炎且能激活ERK通路的最小IL-1β浓度;根据筛选的IL-1β浓度,将髁突软骨细胞随机分为3组:对照组、IL-1β组、IL-1β+ERK抑制剂组。检测各组ERK、Sox-9、COL2的mRNA表达及ERK、P-ERK、Sox-9和COL2的蛋白表达。 结果 培养传代的细胞形态与原代细胞相同,经免疫组化分析为髁突软骨细胞;用10ng/mL的IL-1β处理髁突软骨细胞,P-ERK的表达升高(P<0.05),Sox-9和COL2的表达降低(P均<0.05);与IL-1β组比较, IL-1β+抑制剂组的P-ERK表达被抑制(P<0.05),Sox-9和COL2表达升高(P均<0.05)。 结论 IL-1β能够通过激活ERK通路来抑制大鼠髁突软骨细胞Sox-9 和COL2的表达。
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[1] Elders MJ. The increasing impact of arthritis on public health [J]. J Rheumatol Suppl, 2000, 60: 6-8. [2] Wang XD, Kou XX, He DQ. et al. Progression of cartilage degradation, bone resorption and pain in rat temporomandibular joint osteoarthritis induced by injection of iodoacetate [J]. PLoS One, 2012, 7(9): e45036. doi: 10.1371/journal.pone.0045036. [3] Zhang J, Jiao K, Zhang M. et al. Occlusal effects on longitudinal bone alterations of the temporomandibular joint [J]. J Dent Res, 2013, 92(3): 253-259. [4] DeLise AM, Fischer L, Tuan RS. Cellular interactions and signaling in cartilage development [J]. Osteoarthritis Cartilage, 2000, 8(5): 309-334. [5] Hussein MR, Fathi NA, El-Din AM. et al. Alterations of the CD4(+), CD8(+)T cell subsets, interleukins-1beta, IL-10, IL-17, tumor necrosis factor-alpha and soluble intercellular adhesion molecule-1 in rheumatoid arthritis and osteoarthritis: preliminary observations [J]. Pathol Oncol Res, 2008, 14(3): 321-328. [6] Joosten LA, Helsen MM, Saxne T, et al. IL-1 alpha beta blockade prevents cartilage and bone destruction in murine type II collagen-induced arthritis, whereas TNF-alpha blockade only ameliorates joint inflammation [J]. J Immunol, 1999, 163(9): 5049-5055. [7] Ghivizzani SC, Lechman ER, Kang R. et al. Direct adenovirus-mediated gene transfer of interleukin 1 and tumor necrosis factor alpha soluble receptors to rabbit knees with experimental arthritis has local and distal anti-arthritic effects [J]. Proc Natl Acad Sci U S A, 1998, 95(8): 4613-4618. [8] Orrenius S. Reactive oxygen species in mitochondria-mediated cell death [J]. Drug Metab Rev, 2007, 39(2-3): 443-455. [9] Yasuhara R, Miyamoto Y, Akaike T. et al. Interleukin-1beta induces death in chondrocyte-like ATDC5 cells through mitochondrial dysfunction and energy depletion in a reactive nitrogen and oxygen species-dependent manner [J]. Biochem J, 2005, 389(Pt2): 315-323. [10] Maryu G, Matsuda M, Aoki K. Multiplexed fluorescence imaging of ERK and akt activities and cell-cycle progression [J]. Cell Struct Funct, 2016, 41(2): 81-92. [11] Charlier E, Relic B, Deroyer C. et al. Insights on molecular mechanisms of chondrocytes death in osteoarthritis [J]. Int J Mol Sci, 2016, 17(12): E2146. doi: 10.3390/ijms17122146. [12] Fukuoka Y, Hagihara M, Nagatsu T. et al. The relationship between collagen metabolism and temporomandibular joint osteoarthrosis in mice [J]. J Oral Maxillofac Surg, 1993, 51(3): 288-291. [13] Akiyama H. Control of chondrogenesis by the transcription factor Sox9 [J]. Mod Rheumatol, 2008, 18(3): 213-219. [14] Han Y, Lefebvre V. L-Sox5 and Sox6 drive expression of the aggrecan gene in cartilage by securing binding of Sox9 to a far-upstream enhancer [J]. Mol Cell Biol, 2008, 28(16): 4999-5013. [15] Funato S, Yasuhara R, Yoshimura K, et al. Extracellular matrix loss in chondrocytes after exposure to interleukin-1beta in NADPH oxidase-dependent manner [J]. Cell Tissue Res, 2017, 368(1): 135-144. [16] Maldonado M, Nam J. The role of changes in extracellular matrix of cartilage in the presence of inflammation on the pathology of osteoarthritis [J]. Biomed Res Int, 2013, 2013: 284873. doi: 10.1155/2013/284873. [17] Akutsu M, Ogura N, Ito K. et al. Effects of interleukin-1β and tumor necrosis factor-α on macrophage inflammatory protein-3α production in synovial fibroblast-like cells from human temporomandibular joints [J]. J Oral Pathol Med, 2013, 42(6): 491-498. [18] Mahli A, Saugspier M, Koch A. et al. ERK activation and autophagy impairment are central mediators of irinotecan-induced steatohepatitis [J]. Gut, 2018, 67(4): 746-756. [19] Dong Y, Wu G, Zhu T, et al. VEGF promotes cartilage angiogenesis by phospho-ERK1/2 activation of Dll4 signaling in temporomandibular joint osteoarthritis caused by chronic sleep disturbance in Wistar rats [J]. Oncotarget, 2017, 8(11): 17849-17861. [20] Ma C, Wu G, Wang Z. et al. Effects of chronic sleep deprivation on the extracellular signal-regulated kinase pathway in the temporomandibular joint of rats [J]. PLoS One, 2014, 9(9): e107544. doi: 10.1371/journal.pone.0107544. [21] Guma M, Firestein GS. c-Jun N-terminal kinase in inflammation and rheumatic diseases [J]. Open Rheumatol J, 2012, 6: 220-231. doi: 10.2174/1874312901206010220. [22] Chen J, Wu G, Zhu G, et al. Influence of sleep deprivation on expression of MKK4 and c-fos in the mandibular condylar cartilage of rats [J]. Br J Oral Maxillofac Surg, 2013, 51(8): e250-255. doi: 10.1016/j.bjoms.2013.06.010. [23] Yang HJ, Ju F, Guo XX. et al. RNA-binding protein RBM3 prevents NO-induced apoptosis in human neuroblastoma cells by modulating p38 signaling and miR-143 [J]. Sci Rep, 2017, 7: 41738. doi: 10.1038/srep41738. [24] Wang P, Zhu F, Konstantopoulos K. The antagonistic actions of endogenous interleukin-1β and 15-deoxy-Δ12,14-prostaglandin J2 regulate the temporal synthesis of matrix metalloproteinase-9 in sheared chondrocytes [J]. J Biol Chem, 2012, 287(38): 31877-31893. [25] Su JY, Chen SH, Chen YP. et al. Evaluation of Magnetic Nanoparticle-Labeled Chondrocytes Cultivated on a Type II Collagen-Chitosan/Poly(Lactic-co-Glycolic)Acid Biphasic Scaffold [J]. Int J Mol Sci, 2017, 18(1): E87. doi: 10.3390/ijms18010087. |
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