Amino Acids

, Volume 35, Issue 1, pp 123–127 | Cite as

Recombinant tissue metalloproteinase inhibitor-3 protein induces apoptosis of murine osteoblast MC3T3-E1

  • L.-Q. Yuan
  • Y.-S. Liu
  • X.-H. Luo
  • L.-J. Guo
  • H. Xie
  • Y. Lu
  • X.-P. Wu
  • E.-Y. Liao
Article

Summary.

Tissue inhibitor of metalloproteinases (TIMPs) plays an essential role in the regulation of bone metabolism. Here we report that recombinant tissue metalloproteinase inhibitor-3 (TIMP-3) protein induces the apoptosis of MC3T3-E1 osteoblasts. Cell apoptosis was detected by sandwich-enzyme-immunoassay. Fas and Fasl protein levels were determined by Western blot analysis. The enzyme substrate was used to assess the activation of caspase-3 and caspase-8. The phosphorylation of JNK, p38 and ERK1/2 was examined by Western blot analysis. The ELISA suggested that TIMP-3 promoted MC3T3-E1 cell apoptosis. TIMP-3 treatment induced the expression of Fas and Fasl proteins, and the activation of caspase-8 and caspase-3. TIMP-3 treatment induced p38 and ERK phosphorylation. SB203580 and PD98059, the inhibitor of p38 and ERK, respectively, abolished the TIMP-3 effect on osteoblast apoptosis. In conclusion, the signal pathway through which TIMP-3 induces MC3T3-E1 cell apoptosis, mediated by Fas and involves the p38 and ERK signal transduction pathways.

Keywords: Tissue metalloproteinase inhibitor-3 – Osteoblast – Apoptosis 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Ahonen, M, Poukkula, M, Baker, AH, Kashiwagi, M, Nagase, H, Eriksson, JE, Kahari, VM 2003Tissue inhibitor of metalloproteinases-3 induces apoptosis in melanoma cells by stabilization of death receptorsOncogene2221212134PubMedCrossRefGoogle Scholar
  2. Bond, M, Murphy, G, Bennett, MR, Newby, AC, Baker, AH 2002Tissue inhibitor of metalloproteinase-3 induces a Fas-associated death domain-dependent type II apoptotic pathwayJ Biol Chem2771378713795PubMedCrossRefGoogle Scholar
  3. Brixen, KT, Christensen, PM, Ejersted, C, Langdahl, BL 2004Teriparatide (biosynthetic human parathyroid hormone 1–34): a new paradigm in the treatment of osteoporosisBasic Clin Pharmacol Toxicol94260270PubMedGoogle Scholar
  4. Deng, X, Bhagat, S, Dong, Z, Mullins, C, Chinni, SR, Cher, M 2006Tissue inhibitor of metalloproteinase-3 induces apoptosis in prostate cancer cells and confers increased sensitivity to paclitaxelEur J Cancer4232673273PubMedCrossRefGoogle Scholar
  5. Ding, WX, Ni, HM, DiFrancesca, D, Stolz, DB, Yin, XM 2004Bid-dependent generation of oxygen radicals promotes death receptor activation-induced apoptosis in murine hepatocytesHepatology40403413PubMedCrossRefGoogle Scholar
  6. Drynda, A, Quax, PH, Neumann, M, van der Laan, WH, Pap, G, Drynda, S, Meinecke, I, Kekow, J, Neumann, W, Huizinga, TW, Naumann, M, König, W, Pap, T 2005Gene transfer of tissue inhibitor of metalloproteinases-3 reverses the inhibitory effects of TNF-alpha on Fas-induced apoptosis in rheumatoid arthritis synovial fibroblastsJ Immunol17465246531PubMedGoogle Scholar
  7. Hock, JM, Krishnan, V, Onyia, JE, Bidwell, JP, Milas, J, Stanislaus, D 2001Osteoblast apoptosis and bone turnoverJ Bone Miner Res16975984PubMedCrossRefGoogle Scholar
  8. Jilka, RL, Weinstein, RS, Bellido, T, Roberson, P, Parfitt, AM, Manolagas, SC 1999Increased bone formation by prevention of osteoblast apoptosis with parathyroid hormoneJ Clin Invest104439446PubMedCrossRefGoogle Scholar
  9. Liao, EY, Luo, XH 2001Effect of 17β-estradiol on the expression of matrix metalloproteinase-1, -2 and tissue inhibitor of metalloproteinase-1 in human osteoblast-like cells culturesEndocrine15291295PubMedCrossRefGoogle Scholar
  10. Majid, MA, Smith, VA, Easty, DL, Baker, AH, Newby, AC 2002Adenovirus mediated gene delivery of tissue inhibitor of metalloproteinases-3 induces death in retinal pigment epithelial cellsBr J Ophthalmol8697101PubMedCrossRefGoogle Scholar
  11. Manolagas, SC 2000Birth and death of bone cells: basic regulatory mechanisms and implications for the pathogenesis and treatment of osteoporosisEndocr Rev21115137PubMedCrossRefGoogle Scholar
  12. Mogi, M, Ozeki, N, Nakamura, H, Togari, A 2004Dual roles for NF-kappaB activation in osteoblastic cells by serum deprivation: osteoblastic apoptosis and cell-cycle arrestBone35507516PubMedCrossRefGoogle Scholar
  13. Nagase, H, Woessner, JF,Jr 1999Matrix metalloproteinasesJ Biol Chem2742149121494PubMedCrossRefGoogle Scholar
  14. Span, PN, Lindberg, RL, Manders, P, Tjan-Heijnen, VC, Heuvel, JJ, Beex, LV, Sweep, CG 2004Tissue inhibitors of metalloproteinase expression in human breast cancer: TIMP-3 is associated with adjuvant endocrine therapy successJ Pathol202395402PubMedCrossRefGoogle Scholar
  15. Suzuki, H, Nezaki, Y, Kuno, E, Sugiyama, I, Mizutani, A, Tsukagoshi, N 2003Functional roles of the tissue inhibitor of metalloproteinase 3 (TIMP-3) during ascorbate-induced differentiation of osteoblastic MC3T3-E1 cellsBiosci Biotechnol Biochem6717371743PubMedCrossRefGoogle Scholar
  16. Tanaka, Y, Nakayamada, S, Fujimoto, H, Okada, Y, Umehara, H, Kataoka, T, Minami, Y 2002H-Ras/mitogen-activated protein kinase pathway inhibits integrin-mediated adhesion and induces apoptosis in osteoblastsJ Biol Chem2772144621452PubMedCrossRefGoogle Scholar
  17. Weinstein, RS, Jilka, RL, Parfitt, AM, Manolagas, SC 1998Inhibition of osteoblastogenesis and promotion of apoptosis of osteoblasts and osteocytes by glucocorticoids. Potential mechanisms of their deleterious effects on boneJ Clin Invest102274282PubMedCrossRefGoogle Scholar
  18. Weinstein, RS, Nicholas, RW, Manolagas, SC 2000Apoptosis of osteocytes in glucocorticoid-induced osteonecrosis of the hipJ Clin Endocrinol Metab8529072012PubMedCrossRefGoogle Scholar
  19. Yuan, LQ, Lu, Y, Luo, XH, Xie, H, Wu, XP, Liao, EY 2007Taurine promotes connective tissue growth factor (CTGF) expression in osteoblasts through the ERK signal pathwayAmino Acids32425430PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • L.-Q. Yuan
    • 1
  • Y.-S. Liu
    • 2
  • X.-H. Luo
    • 1
  • L.-J. Guo
    • 1
  • H. Xie
    • 1
  • Y. Lu
    • 1
  • X.-P. Wu
    • 1
  • E.-Y. Liao
    • 1
  1. 1.Institute of Metabolism and Endocrinology, The Second Xiangya HospitalCentral South UniversityChangshaChina
  2. 2.Geriatric Department of the Second Xiangya HospitalCentral South UniversityChangshaChina

Personalised recommendations