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July-2015 Volume 12 Issue 1

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Article

Arg972 insulin receptor substrate‑1 enhances tumor necrosis factor‑α‑induced apoptosis in osteoblasts

  • Authors:
    • Yunhui You
    • Shiqing Liu
    • Lijuan Peng
    • Mei Long
    • Hongxiang Deng
    • Hongjun Zhao
  • View Affiliations / Copyright

    Affiliations: Department of Rheumatology and Immunology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China
  • Pages: 255-260
    |
    Published online on: March 9, 2015
       https://doi.org/10.3892/mmr.2015.3457
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Abstract

The presence of Arg972 insulin receptor substrate‑1 (IRS‑1) is associated with impaired insulin/IRS‑1 signaling to activate phosphatidylinositol‑3 kinase (PI3K). Tumor necrosis factor‑α (TNF‑α), an inflammatory cytokine with a central role in the pathogenesis of rheumatoid arthritis (RA), induces apoptosis in osteoblasts, which are the principal cell type responsible for bone loss in RA. In our previous study, an association between Arg972 IRS‑1 and a high risk and severity of RA was identified. In the present study, the effects of Arg972 IRS‑1 and IRS‑1 on TNF‑α‑induced apoptosis in human osteoblasts were examined. Normal and RA osteoblasts were stably transfected with Arg972 IRS‑1 and IRS‑1. In addition, cells were stably transduced with IRS‑1‑shRNA to knock down IRS‑1. Following stimulation with 10 nM insulin for 30 min, the stable overexpression of Arg972 IRS‑1 and knock down of IRS‑1 significantly decreased IRS‑1‑associated PI3K activity and Akt activation/phosphorylation at serine 473 (ser473) and enhanced TNF‑α‑induced apoptosis in normal and in RA osteoblasts. By contrast, the stable overexpression of IRS‑1 significantly increased the levels of IRS‑1‑associated PI3K activity and Akt phosphorylation (ser473) and inhibited TNF‑α‑induced apoptosis, which was eliminated by pretreatment with 50 µn BJM120, a selective PI3K inhibitor, for 30 min. In conclusion, the present study provided the first evidence, to the best of our knowledge, that insulin stimulation of Arg972 IRS‑1 and IRS‑1 enhanced and inhibited TNF‑α‑induced apoptosis, respectively in normal and RA osteoblasts by a PI3K‑dependent mechanism. These findings suggest that insulin/IRS‑1 signaling is important in the pathogenesis of RA.
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1 

Zeng G, Nystrom FH, Ravichandran LV, Cong LN, Kirby M, Mostowski H and Quon MJ: Roles for insulin receptor, PI3-kinase, and Akt in insulin signaling pathways related to production of nitric oxide in human vascular endothelial cells. Circulation. 101:1539–1545. 2000. View Article : Google Scholar : PubMed/NCBI

2 

Kuboki K, Jiang ZY, Takahara N, et al: Regulation of endothelial constitutive nitric oxide synthase gene expression in endo-thelial cells and in vivo: a specific vascular action of insulin. Circulation. 101:676–681. 2000. View Article : Google Scholar : PubMed/NCBI

3 

Fallucca F, Dalfrà MG, Sciullo E, et al: Polymorphisms of insulin receptor substrate 1 and beta3-adrenergic receptor genes in gestational diabetes and normal pregnancy. Metabolism. 55:1451–1456. 2006. View Article : Google Scholar : PubMed/NCBI

4 

Huang C, Lin Z, Zhou Y, et al: Arg(972) insulin receptor substrate-1 is associated with elevated plasma endothelin-1 level in hypertensives. J Hypertens. 30:1751–1757. 2012. View Article : Google Scholar : PubMed/NCBI

5 

Zhao H, Liu S, Long M, Peng L, Deng H and You Y: Arg972 Insulin receptor substrate-1 polymorphism and risk and severity of rheumatoid arthritis. J Int Rheum Dis. In press.

6 

Nanke Y, Kotake S, Akama H and Kamatani N: Alkaline phosphatase in rheumatoid arthritis patients: possible contribution of bone-type ALP to the raised activities of ALP in rheumatoid arthritis patients. Clin Rheumatol. 21:198–202. 2002. View Article : Google Scholar : PubMed/NCBI

7 

Neve A, Corrado A and Cantatore FP: Osteoblast physiology in normal and pathological conditions. Cell Tissue Res. 343:289–302. 2011. View Article : Google Scholar

8 

Fütterer A, Mink K, Luz A, Kosco-Vilbois MH and Pfeffer K: The lymphotoxin beta receptor controls organogenesis and affinity maturation in peripheral lymphoid tissues. Immunity. 9:59–70. 1998. View Article : Google Scholar : PubMed/NCBI

9 

McInnes IB and Liew FY: Cytokine networks: Towards new therapies for rheumatoid arthritis. Nat Clin Prac Rheumatol. 1:31–39. 2005. View Article : Google Scholar

10 

Kitajima I, Soejima Y, Takasaki I, Beppu H, Tokioka T and Maruyama I: Ceramide-induced nuclear translocation of NFkappa B is a potential mediator of the apoptotic response to TNF-alpha in murine clonal osteoblasts. Bone. 19:263–270. 1996. View Article : Google Scholar : PubMed/NCBI

11 

Hill PA, Tumber A and Meikle MC: Multiple extracellular signals promote osteoblast survival and apoptosis. Endocrinology. 138:3849–3858. 1997.PubMed/NCBI

12 

Jilka RL, Weinstein RS, Bellido T, Parfitt AM and Manolagas SC: Osteoblast programmed cell death (apoptosis): Modulation by growth factors and cytokines. J Bone Miner Res. 13:793–802. 1998. View Article : Google Scholar : PubMed/NCBI

13 

Hock JM, Krishnan V, Onyia JE, Bidwell JP, Milas J and Stanislaus D: Osteoblast apoptosis and bone turnover. J Bone Miner Res. 16:975–984. 2001. View Article : Google Scholar : PubMed/NCBI

14 

Chen L, Monti S, Juszczynski P, et al: SYK inhibition modulates distinct PI3K/AKT- dependent survival pathways and cholesterol biosynthesis in diffuse large B cell lymphomas. Cancer Cell. 23:826–838. 2013. View Article : Google Scholar : PubMed/NCBI

15 

Porzio O, Federici M, Hribal ML, et al: The Gly972-->Arg amino acid polymorphism in IRS-1 impairs insulin secretion in pancreatic beta cells. J Clin Invest. 104:357–364. 1999. View Article : Google Scholar : PubMed/NCBI

16 

Nagoshi T, Matsui T, Aoyama T, et al: PI3K rescues the detrimental effects of chronic Akt activation in the heart during ischemia/reperfusion injury. J Clin Invest. 115:2128–2138. 2005. View Article : Google Scholar : PubMed/NCBI

17 

Matsui T, Li L, del Monte F, Fukui Y, Franke TF, Hajjar RJ and Rosenzweig A: Adenoviral gene transfer of activated PI 3-kinase and Akt inhibits apoptosis of hypoxic cardiomyocytes in vitro. Circulation. 100:2373–2379. 1999. View Article : Google Scholar : PubMed/NCBI

18 

Yang J, Zhang X, Wang W and Liu J: Insulin stimulates osteoblast proliferation and differentiation through ERK and PI3K in MG-63 cells. Cell Biochem Funct. 28:334–341. 2010. View Article : Google Scholar

19 

Byun CH, Koh JM, Kim DK, Park SI, Lee KU and Kim GS: α-lipoic acid inhibits TNF-α-induced apoptosis in human bone marrow stromal cells. J Bone Miner Res. 20:1125–1135. 2005. View Article : Google Scholar : PubMed/NCBI

20 

Ma X and Xu S: TNF inhibitor therapy for rheumatoid arthritis (Review). Biomed Rep. 1:177–184. 2013.

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Copy and paste a formatted citation
Spandidos Publications style
You Y, Liu S, Peng L, Long M, Deng H and Zhao H: Arg972 insulin receptor substrate‑1 enhances tumor necrosis factor‑α‑induced apoptosis in osteoblasts. Mol Med Rep 12: 255-260, 2015.
APA
You, Y., Liu, S., Peng, L., Long, M., Deng, H., & Zhao, H. (2015). Arg972 insulin receptor substrate‑1 enhances tumor necrosis factor‑α‑induced apoptosis in osteoblasts. Molecular Medicine Reports, 12, 255-260. https://doi.org/10.3892/mmr.2015.3457
MLA
You, Y., Liu, S., Peng, L., Long, M., Deng, H., Zhao, H."Arg972 insulin receptor substrate‑1 enhances tumor necrosis factor‑α‑induced apoptosis in osteoblasts". Molecular Medicine Reports 12.1 (2015): 255-260.
Chicago
You, Y., Liu, S., Peng, L., Long, M., Deng, H., Zhao, H."Arg972 insulin receptor substrate‑1 enhances tumor necrosis factor‑α‑induced apoptosis in osteoblasts". Molecular Medicine Reports 12, no. 1 (2015): 255-260. https://doi.org/10.3892/mmr.2015.3457
Copy and paste a formatted citation
x
Spandidos Publications style
You Y, Liu S, Peng L, Long M, Deng H and Zhao H: Arg972 insulin receptor substrate‑1 enhances tumor necrosis factor‑α‑induced apoptosis in osteoblasts. Mol Med Rep 12: 255-260, 2015.
APA
You, Y., Liu, S., Peng, L., Long, M., Deng, H., & Zhao, H. (2015). Arg972 insulin receptor substrate‑1 enhances tumor necrosis factor‑α‑induced apoptosis in osteoblasts. Molecular Medicine Reports, 12, 255-260. https://doi.org/10.3892/mmr.2015.3457
MLA
You, Y., Liu, S., Peng, L., Long, M., Deng, H., Zhao, H."Arg972 insulin receptor substrate‑1 enhances tumor necrosis factor‑α‑induced apoptosis in osteoblasts". Molecular Medicine Reports 12.1 (2015): 255-260.
Chicago
You, Y., Liu, S., Peng, L., Long, M., Deng, H., Zhao, H."Arg972 insulin receptor substrate‑1 enhances tumor necrosis factor‑α‑induced apoptosis in osteoblasts". Molecular Medicine Reports 12, no. 1 (2015): 255-260. https://doi.org/10.3892/mmr.2015.3457
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