Interleukin-1 and Tumor Necrosis Factor Activities Partially Account for Calvarial Bone Resorption Induced by Local Injection of Lipopolysaccharide

ABSTRACT The present study was undertaken to test the hypothesis that tumor necrosis factor (TNF) and/or interleukin-1 (IL-1) activity mediates lipopolysaccharide (LPS)-induced bone resorption in vivo. To test this hypothesis, Escherichia coli LPS or Porphyromonas gingivalis LPS was injected into the subcutaneous tissues overlying mouse calvariae. Histological sections, prepared from the center of the lesion, were stained for tartrate-resistant acid phosphatase, and histomorphometric analysis was performed to quantify the osteoclast number and the area of bone resorption. In time course experiments using normal mice, a peak of bone resorption occurred 5 days after endotoxin stimulation. In dose-response experiments, IL-1 receptor type 1 deletion (IL-1R−/−), TNF double-receptor p55/p75 deletion (TNF p55−/−/p75−/−), combined TNF p55 and IL-1 receptor type 1 deletion (TNF p55−/−/IL-1R−/−), and IL-1β-converting enzyme-deficient (ICE−/−) mice and the respective wild-type mice were injected with 500, 100, or 20 μg of P. gingivalis LPS and sacrificed 5 days after LPS injection. At the highest dose (500 μg), significant decreases in osteoclast number occurred in mutant mice compared to wild-type mice: (i) a 64% reduction for the TNF p55−/−/IL-1R−/− mice, (ii) a 57% reduction for the IL-1R−/− mice, (iii) a 41% reduction for the TNF p55−/−/p75−/− mice, and (iv) a 38% reduction for the ICE−/− mice. At the two lower doses, bone resorption was apparent but no significant differences between mutant and wild-type animals were observed. The present data indicate that at higher doses, LPS-induced bone resorption is substantially mediated by IL-1 and TNF receptor signaling. Furthermore, IL-1 receptor signaling appears to be slightly more important than TNF receptor signaling. At lower LPS doses, other pathways leading to osteoclast activity that are independent of TNF and IL-1 are involved.

[1]  K. Simon,et al.  Lipopolysaccharide from Actinobacillus actinomycetemcomitans stimulates macrophages to produce interleukin-1 and tumor necrosis factor mRNA and protein. , 2007, Oral microbiology and immunology.

[2]  D. Graves,et al.  Interleukin-1 and tumor necrosis factor antagonists inhibit the progression of inflammatory cell infiltration toward alveolar bone in experimental periodontitis. , 1998, Journal of periodontology.

[3]  L. Kesavalu,et al.  Bone Resorption Caused by Three Periodontal Pathogens In Vivo in Mice Is Mediated in Part by Prostaglandin , 1998, Infection and Immunity.

[4]  C. Ware,et al.  TNF receptor-deficient mice reveal divergent roles for p55 and p75 in several models of inflammation. , 1998, Journal of immunology.

[5]  D. Graves,et al.  IL-1 and TNF antagonists inhibit the inflammatory response and bone loss in experimental periodontitis. , 1998, Journal of immunology.

[6]  J. Peschon,et al.  Antiviral Activity of Tumor Necrosis Factor (TNF) Is Mediated via p55 and p75 TNF Receptors , 1997, The Journal of experimental medicine.

[7]  P. Morrissey,et al.  Phenotypic and functional characterization of mice that lack the type I receptor for IL-1. , 1997, Journal of immunology.

[8]  S. Teitelbaum,et al.  Lipopolysaccharide-stimulated osteoclastogenesis is mediated by tumor necrosis factor via its P55 receptor. , 1997, The Journal of clinical investigation.

[9]  T. Takata,et al.  Reactive change in proliferative activity of the junctional epithelium after topical application of lipopolysaccharide. , 1997, Journal of periodontology.

[10]  R. Schreiber,et al.  Constitutive shedding of both p55 and p75 murine TNF receptors in vivo. , 1997, Journal of immunology.

[11]  Roodman Gd.  Advances in bone biology: the osteoclast. , 1996, Endocrine reviews.

[12]  T. Suzuki,et al.  In vivo administration of IL-1 beta accelerates silk ligature-induced alveolar bone resorption in rats. , 1995, Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology.

[13]  R. Kimble,et al.  Simultaneous block of interleukin-1 and tumor necrosis factor is required to completely prevent bone loss in the early postovariectomy period. , 1995, Endocrinology.

[14]  N. Piesco,et al.  Differential Expression of IL-1β, TNF-α, IL-6, and IL-8 in Human Monocytes in Response to Lipopolysaccharides from Different Microbes , 1995 .

[15]  R. Kamen,et al.  Mice deficient in IL-1β-converting enzyme are defective in production of mature IL-1β and resistant to endotoxic shock , 1995, Cell.

[16]  G. Mundy,et al.  Use of an in vivo model to determine the effects of interleukin‐1 on cells at different stages in the osteoclast lineage , 1995, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[17]  G. Passeri,et al.  Interleukin-11: a new cytokine critical for osteoclast development. , 1994, The Journal of clinical investigation.

[18]  S. Amar,et al.  Porphyromonas gingivalis lipopolysaccharide stimulation of human monocytes: dependence on serum and CD14 receptor. , 1994, Oral microbiology and immunology.

[19]  H. Birkedal‐Hansen.  Role of cytokines and inflammatory mediators in tissue destruction. , 1993, Journal of periodontal research.

[20]  R. Zinkernagel,et al.  Mice lacking the tumour necrosis factor receptor 1 are resistant to IMF-mediated toxicity but highly susceptible to infection by Listeria monocytogenes , 1993, Nature.

[21]  M. Gayle,et al.  Interleukin 1 signaling occurs exclusively via the type I receptor. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[22]  C. Galanos,et al.  Mechanisms of endotoxin shock and endotoxin hypersensitivity. , 1993, Immunobiology.

[23]  M. de Vernejoul,et al.  Local bone injections of LPS and M-CSF increase bone resorption by different pathways in vivo in rats. , 1993, The American journal of physiology.

[24]  T. Martin,et al.  Modulation of osteoclast differentiation. , 1992, Endocrine reviews.

[25]  S. Hamada,et al.  Induction of interleukin-1 and -6 in human gingival fibroblast cultures stimulated with Bacteroides lipopolysaccharides , 1991, Infection and immunity.

[26]  T. Hirano,et al.  IL-6 is produced by osteoblasts and induces bone resorption. , 1990, Journal of immunology.

[27]  E. Burger,et al.  Bacteroides gingivalis stimulates bone resorption via interleukin-1 production by mononuclear cells. The relative role for B. gingivalis endotoxin. , 1990, Journal of clinical periodontology.

[28]  J. Cavaillon,et al.  Lipopolysaccharide-induced production of cytokines by bone marrow-derived macrophages: dissociation between intracellular interleukin 1 production and interleukin 1 release. , 1990, Cytokine.

[29]  Y. Toyama,et al.  Appearance of osteoclasts by injections of lipopolysaccharides in rat periodontal tissue. , 1989, Journal of periodontal research.

[30]  G. Mundy,et al.  Effects of interleukin-1 on bone turnover in normal mice. , 1989, Endocrinology.

[31]  G. Roodman,et al.  Tumors producing human tumor necrosis factor induced hypercalcemia and osteoclastic bone resorption in nude mice. , 1989, Endocrinology.

[32]  C. Chenu,et al.  Interleukin‐1 and tumor necrosis factor stimulate the formation of human osteoclastlike cells in vitro , 1989, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[33]  L. Bonewald,et al.  Infusions of recombinant human interleukins 1 alpha and 1 beta cause hypercalcemia in normal mice. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[34]  M. Drezner,et al.  Bone histomorphometry: Standardization of nomenclature, symbols, and units: Report of the asbmr histomorphometry nomenclature committee , 1987, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[35]  G. Mundy,et al.  Tumor necrosis factors alpha and beta induce osteoblastic cells to stimulate osteoclastic bone resorption. , 1987, Journal of immunology.

[36]  A. C. Webb,et al.  Multiple biological activities of human recombinant interleukin 1. , 1986, The Journal of clinical investigation.

[37]  J. Reynolds,et al.  Stimulation of bone resorption in vitro by a non-prostanoid factor released by human monocytes in culture. , 1983, Biochimica et biophysica acta.

[38]  E. Hausmann,et al.  Human dental plaque: stimulation of bone resorption in tissue culture. , 1973, Archives of oral biology.

[39]  R. B. Parker,et al.  The passage of tritiated bacterial endotoxin across intact gingival crevicular epithelium. , 1972, Journal of periodontology.

[40]  J. B. Gunnison,et al.  Studies on the Antigenic Substances of CL. Botulinum XXXIII , 1929, The Journal of Immunology.

[41]  G. Roodman,et al.  Advances in bone biology: the osteoclast. , 1996, Endocrine reviews.

[42]  M. Paskind,et al.  Mice deficient in IL-1 beta-converting enzyme are defective in production of mature IL-1 beta and resistant to endotoxic shock. , 1995, Cell.

[43]  H. Bluethmann,et al.  Tumor necrosis factor (TNF)-induced cutaneous necrosis is mediated by TNF receptor 1. , 1995, Journal of inflammation.

[44]  N. Piesco,et al.  Differential expression of IL-1 beta, TNF-alpha, IL-6, and IL-8 in human monocytes in response to lipopolysaccharides from different microbes. , 1995, Journal of dental research.

[45]  H. J. Sismey-Durrant,et al.  The effect of lipopolysaccharide from the oral bacterium Bacteroides gingivalis on osteoclastic resorption of sperm-whale dentine slices in vitro. , 1987, Archives of oral biology.

[46]  O. Westphal.  Bacterial lipopolysaccharides : extraction with phenol-water and further applications of the procedure , 1965 .