Effects of Interleukin-1${\beta}$ and Tumor Necrosis $Factor-{\alpha}$ on the Release of Collagenase and Gelatinase from Osteoblasts

  • Eun, Jong-Gab (Departments of Dental Pharmacology, School of Dentistry, Dankook University) ;
  • Baek, Dong-Heon (Departments of Oral Microbiology and Immunology, School of Dentistry, Dankook University) ;
  • Kim, Se-Won (Departments of Dental Pharmacology, School of Dentistry, Dankook University)
  • Published : 2002.10.21

Abstract

A large number of factors such as osteotropic hormones, cytokines, or growth factors are related to the bone remodeling which is characterized by the coupling of osteoclast-mediated bone resorption and osteoblast-mediated bone formation. Recent investigations have indicated that cytokines such as $interleukin-1{\beta}\;(IL-1{\beta})$ and tumor necrosis $factor-{\alpha}\;(TNF-{\alpha})$ play a potential role in the bone resorption associated with a variety of pathological conditions such as inflammatory osteolytic disease. Collagen is the most abundant protein of the extracellular matrix of bone, and the participation of collagenase in bone resorption has been widely investigated. In this study, effects of $IL-1{\beta}$ and $TNF-{\alpha}$ on the release of collagenase from osteoblastic cells were measured. The gelatinase activity was also measured by gel substrate analysis (zymography) after electrophoresis of conditioned media of osteoblastic cell culture. $IL-1{\beta}$ increased the collagenase activity in ROS17/2.8 and HOS cell culture. $TNF-{\alpha}$ also increased the collagenase activity of osteoblastic cells. When two kinds of cytokines were treated simultaneously in the culture of osteoblastic cells, synergistic increase of collagenase activity was seen in ROS17/2.8 cells. $IL-1{\beta}$ and $TNF-{\alpha}$ significantly increased the collagenase activity after 6 hour treatment in the osteoblastic cell culture, and there was no additional increase according to the culture period. Osteoblastic cells released the gelatinase and molecular weight of this enzyme was measured about 70 KDa as assessed by zymogram. $IL-1{\beta}$ and $TNF-{\alpha}$ showed increase of the gelatinase activity produced by ROS17/2.8 and HOS cells. Taken together, this study suggested that $IL-1{\beta}$ and $TNF-{\alpha}$ can modulate bone metabolism, at least in part, by increased release of collagenase and gelatinase from osteoblasts.

Keywords

References

  1. Aarden LA, Brunner TK, Cerottini JC. Revised nomenclature for antigen-nonspecific T cell proliferation and helper factors. J Immunol 123: 2928-2929, 1979
  2. Bertolini DR, Nedwin GE, Bringman TS, Smith DD, Mundy GR. Stimulation of bone resorption and inhibition of bone formation in vitro by human tumor necrosis factors. Nature 319: 516-518, 1986 https://doi.org/10.1038/319516a0
  3. Callaghan MM, Lovis RM, Rammohan C, Lu Y, Pope RM. Autocrine regulation of collagenase gene expression by TNF-alpha in U937 cells. J Leukoc Biol 59: 125-132, 1996 https://doi.org/10.1002/jlb.59.1.125
  4. Cohen-Solal ME, Graulet AM, Denne MA, Gueris J, Baylink D, de Vernejoul MC. Peripheral monocyte culture supernatants of menopausal women can induce bone resorption: involvement of cytokines. J Clin Endocrinol Metab 77: 1648-1653, 1993 https://doi.org/10.1210/jc.77.6.1648
  5. Dayer JM, Robinson DR, Krane SM. Prostaglandin production by rheumatoid synovial cells: Stimulation by a factor from human mononuclear cells. J Exp Med 145: 1399-1404, 1977 https://doi.org/10.1084/jem.145.5.1399
  6. Delaisse JM, Eeckhout Y, Vaes G. Bone resorbing agents affect the production and distribution of procollagenase as well as the activity of collagenase in bone tissue. Endocrinology 123: 264-276, 1988 https://doi.org/10.1210/endo-123-1-264
  7. Dewhirst FE, Stashenko PP, Mole JE, Tsurumachi T. Purification and partial sequence of human osteoclast-activating factor: identity with interleukin 1 beta. J Immunol 135: 2562-2568, 1985
  8. Ducy P, Schinke T, Karsenty G. The osteoblasts: A sophisticated fibroblast under central surveillance. Science 289: 1501-1504, 2000 https://doi.org/10.1126/science.289.5484.1501
  9. Garrett R, Durie BGM, Nedwin GB, Gillespie A, Bringman T, Sabatini M, Bertolini DR, Mundy GR. Production of lymphotoxin, a bone-resorbing cytokine by cultured human myeloma cells. N Eng J Med 317: 526-532, 1987 https://doi.org/10.1056/NEJM198708273170902
  10. Gowen M, Wood DD, Ihrie EJ, McGuire MKB, Russell RGG. An interleukin 1 like factor stimulates bone resorption in vitro. Nature 306: 378-380, 1983 https://doi.org/10.1038/306378a0
  11. Gowen M, Wood DD, Ihrie EJ, Meats JE, Russell RG. Stimulation by human interleukin-1 of cartilage breakdown and production of collagenase and proteoglycanase by human chondrocytes but not by human osteoblasts in vitro. Biochim Biophys Acta 797: 186-193, 1984 https://doi.org/10.1016/0304-4165(84)90121-1
  12. Heath JK, Atkinson SJ, Meikle MC, Reynolds JJ. Mouse osteoblasts synthesize collagenase in response to bone resorbing agents. Biochim Biophys Acta 802: 151-154, 1984 https://doi.org/10.1016/0304-4165(84)90046-1
  13. Hofbauer LC, Lacey DL, Dunstan CR, Spelsberg TC, Riggs BL, Khosla S. Interleukin-1$\beta$ and tumor necrosis factor-$\alpha$ but not interleukin-6, stimulate osteoprotegerin ligand gene expression in human ostoblastic cells. Bone 25: 255-259, 1999 https://doi.org/10.1016/S8756-3282(99)00162-3
  14. Horton JE, Raisz LG, Simmons HA, Oppenheim JJ, Mergenhagen SE. Bone resorbing activity in supernatant fluid from human cultured peripheral blood leukocytes. Science 177: 793-795, 1972 https://doi.org/10.1126/science.177.4051.793
  15. Jilka RL, Hamilton JW. Evidence for two pathways for stimulation of collagenolysis in bone. Calcif Tissue Int 37: 300-306, 1985 https://doi.org/10.1007/BF02554878
  16. Johnson RA, Boyce BF, Mundy GR, Roodman GD. Tumors producing human tumor necrosis factor induced hypercalcemia and osteoclastic bone resorption in nude mice. Endocrinology 124: 1424-1427, 1989 https://doi.org/10.1210/endo-124-3-1424
  17. Kimble RB, Matayoshi AB, Vannice JL, Kung V, Williams C, Pacifici R. Simultaneous block of interleukin-1 and tumor necrosis factor is required to completely prevent bone loss in the early postovariectomy period. Endocrinology 136: 3054-3061, 1995 https://doi.org/10.1210/en.136.7.3054
  18. Konig A, Muhlbauer RC, Fleisch H. Tumor necrosis factor $\alpha$ and interleukin-1 stimulate bone resorption in vivo as measured by urinary $[^3H]$ tetracycline excretion from prelabeled mice. J Bone Miner Res 3: 621-627, 1988 https://doi.org/10.1002/jbmr.5650030607
  19. Lomedico PT, Kilian PL, Gubler U, Stern AS, Chizzonite R. Molecular biology of interleukin-1. Cold Spring Harbor Symp Quant Biol 51: 631-639, 1986 https://doi.org/10.1101/SQB.1986.051.01.075
  20. Lorenzo JA, Pilbeam CC, Kalinowski JF, Hibbs MS. Production of both 92- and 72-KDa gelatinase by bone cells. Matrix 12: 282- 290, 1992 https://doi.org/10.1016/S0934-8832(11)80080-6
  21. Maciewicz RA, Etherington DJ. A comparison of four cathepsins (B, L, N and S) with collagenolytic activity from rabbit spleen. Biochem J 256: 433-440, 1988 https://doi.org/10.1042/bj2560433
  22. Meikle MC, Atkinson SJ, Ward RV, Murphy G, Reynolds JJ. Gingival fibroblasts degrade type I collagen films when stimulated with tumor necrosis factor and interleukin 1: evidence that breakdown is mediated by metalloproteinases. J Periodontal Res 24: 207-213, 1989 https://doi.org/10.1111/j.1600-0765.1989.tb02007.x
  23. Meyer FA, Yaron I, Yaron M. Synergistic, additive, and antagonistic effects of interleukin-1 beta, tumor necrosis factor alpha, and gamma-interferon on prostaglandin E, hyaluronic acid, and collagenase production by cultured synovial fibroblasts. Arthritis Rheum 33: 1518-1525, 1990 https://doi.org/10.1002/art.1780331009
  24. Mizel SB, Dayer JM, Krane SM, Mergenhagen SE. Stimulation of rheumatoid synovial cell collagenase and prostaglandin production by partially purified lymphocyte-activating factor (interleukin- 1) Proc Natl Acad Sci USA 78: 2474-2477, 1981 https://doi.org/10.1073/pnas.78.4.2474
  25. Mundy GR. Incidence and pathophysiology of hypercalcemia. Calcif Tissue Int 46 (Suppl. 1): S3-S10, 1990 https://doi.org/10.1007/BF02553287
  26. Mundy GR. Mechanisms of osteolytic bone destruction. Bone 12 (Suppl. 1): S1-S6, 1991 https://doi.org/10.1016/8756-3282(91)90057-P
  27. Nguyen L, Dewhirst FE, Hauschka PV, Stashenko P. Interleukin-1 $\beta$stimulates bone resorption and inhibits bone formation in vivo. Lymphokine Cytokine Res 10: 15-21, 1991
  28. Partridge NC, Jeffrey JJ, Ehlich LS, Teitelbaum SL, Fliszar C, Welgus HG, Kahn AJ. Hormonal regulation of the production of collagenase inhibitor activity by rat osteogenic sarcoma cells. Endocrinology 120: 1956-1962, 1987 https://doi.org/10.1210/endo-120-5-1956
  29. Ralston SH, Russel RG, Gowen M. Estrogen inhibits release of tumor necrosis factor from peripheral blood mononuclear cells in postmenopausal women. J Bone Min Res 5: 983-988, 1990 https://doi.org/10.1002/jbmr.5650050912
  30. Rifas L. Bone and cytokines: Beyond IL-1, IL-6 and TNF-$\alpha$. Calcif Tissue Int 64: 1-7, 1999 https://doi.org/10.1007/s002239900570
  31. Rifas L, Halstead LR, Peck WA, Avioli LV, Welgus HG. Human osteoblasts in vitro secrete tissue inhibitor of metalloproteinases and gelatinase but not interstitial collagenase as major cellular products. J Clin Invest 84: 686-694, 1989 https://doi.org/10.1172/JCI114216
  32. Sakamoto S, Sakamoto M. Degradative processes of connective tissue proteins with special emphasis on collagenolysis and bone resorption. Mol Aspects Med 10: 299-428, 1988 https://doi.org/10.1016/0098-2997(88)90025-8
  33. Saklatvala J. Characterization of catabolin, the major product of synovium that induces resorption of cartilage proteoglycan in vitro. Biochem J 199: 705-714, 1981 https://doi.org/10.1042/bj1990705
  34. Saklatvala J, Pilsworth LMC, Sarsfield SJ, Gavrilovic J, Heath JK. Pig catabolin is a form of interleukin 1. Cartilage and bone resorb, fibroblasts make prostaglandin and collagenase, and thymocyte proliferation is augmented in response to one protein. Biochem J 224: 461-466, 1984 https://doi.org/10.1042/bj2240461
  35. Shen V, Kohler G, Jeffrey JJ, Peck WA. Bone-resorbing agents promote and interferon-gamma inhibits bone cell collagenase production. J Bone Miner Res 3: 657-666, 1988 https://doi.org/10.1002/jbmr.5650030611
  36. Shingu M, Nagai Y, Isayama T, Naono T, Nobunaga M, Nagai Y. The effects of cytokines on metalloproteinase inhibitors (TIMP) and collagenase production by human chondrocytes and TIMP production by synovial cells and endothelial cells. Clin Exp Immunol 94: 145-149, 1993 https://doi.org/10.1111/j.1365-2249.1993.tb05992.x
  37. Suda T, Nakamura I, Jimi E, Takahashi N. Regulation of osteoclast function. J Bone Min Res 12: 869-879, 1997 https://doi.org/10.1359/jbmr.1997.12.6.869
  38. Tatakis DN. Interleukin-1 and bone metabolism: A review. J Periodontol 64: 416-431, 1993
  39. Teitelbaum SL. Bone resorption by osteoclasts. Science 289: 1504-1508, 2000 https://doi.org/10.1126/science.289.5484.1504
  40. Vaes G. Cellular biology and biochemical mechanism of bone resorption. A review of recent developments on the formation, activation and mode of action of osteoclasts. Clin Orthop Rel Res 231: 239-271, 1988