Stimulation of prostaglandin E2 and bone resorption by recombinant human interleukin 1 alpha in fetal mouse bones

Sato, Kanji; Fujii, Yuko; Kasono, Keizo; Saji, Motoyasu; Tsushima, Takahiro; Shizume, Kazuo

doi:10.1016/s0006-291x(86)80541-1

Cited by 133 publications

(46 citation statements)

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“…PGE 2 is produced in bone mainly by osteoblasts and acts as a potent stimulator of bone resorption (37,40,46). It has been demonstrated that PGE 2 can mediate RANK-L-dependent osteoclastogenesis in periodontal diseases (8).…”

Section: Discussionmentioning

confidence: 99%

“…RANK-L is therefore thought to be the essential and final common signal required both in vitro and in vivo for full osteoclastic differentiation from multipotential hematopoietic precursor cells into mature multinucleated bone-resorptive osteoclasts (22,24,25). Thus, osteoblasts can regulate both net bone formation and resorption.Prostaglandin E 2 (PGE 2 ) is produced in bone mainly by osteoblasts and acts as a potent stimulator of bone resorption by inducing osteoclast formation in both mouse bone marrow cultures and calvarial cultures (1,7,37,40,46,48). PGE 2 synthesis is regulated by three metabolic steps: the release of arachidonic acid from the membranous phospholipids by phospholipase A 2 , the conversion of arachidonic acid to prostaglandin H 2 (PGH 2 ) by cyclooxygenase (COX), and the synthesis of PGE 2 catalyzed by PGE synthase (9,20,26,34,42,44,50).…”

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confidence: 99%

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Staphylococcus aureusInduces Expression of Receptor Activator of NF-κB Ligand and Prostaglandin E₂in Infected Murine Osteoblasts

et al. 2008

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Osteomyelitis is an inflammatory disease of the bone that is characterized by the presence of necrotic bone tissue and increased osteoclast activity. Staphylococcus aureus is responsible for approximately 80% of all cases of human osteomyelitis. While the disease is especially difficult to treat, the pathogenesis of S. aureus-induced osteomyelitis is poorly understood. Elucidating the molecular mechanisms by which S. aureus induces osteomyelitis could lead to a better understanding of the disease and its progression and development of new treatments. Osteoblasts can produce several soluble factors that serve to modulate the activity or formation of osteoclasts. Receptor activator of NF-B ligand (RANK-L) and prostaglandin E 2 (PGE 2 ) are two such molecules which can promote osteoclastogenesis and stimulate bone resorption. In addition, previous studies in our laboratory have shown that osteoblasts produce inflammatory cytokines, such as interleukin 6, following infection with S. aureus, which could induce COX-2 and in turn PGE 2 , further modulating osteoclast recruitment and differentiation. Therefore, we hypothesized that following infection with S. aureus, osteoblasts will express increased levels of RANK-L and PGE 2 . The results presented in this study provide evidence for the first time that RANK-L mRNA and protein and PGE 2 expression are upregulated in S. aureus-infected primary osteoblasts. In addition, through the use of the specific COX-2 inhibitor NS 398, we show that when PGE 2 production is inhibited, RANK-L production is decreased. These data suggest a mechanism whereby osteoblasts regulate the production of RANK-L during infection.Osteomyelitis is a severe infection of bone tissue that results in progressive inflammatory destruction of bone (41). The gram-positive organism Staphylococcus aureus is the most common causative agent of osteomyelitis, accounting for approximately 80% of all human cases (27). It is often necessary that infected bone be debrided, tissues reconstructed, and longterm antibiotic therapy utilized (18). The current treatment for osteomyelitis is often traumatic and expensive and often leads to further selection of antibiotic-resistant strains of S. aureus. The growing incidence of antibiotic-resistant S. aureus strains can explain the recurrent attacks of osteomyelitis in patients undergoing therapy. In addition, the pathogenesis of S. aureusinduced osteomyelitis is poorly understood. Elucidating the mechanisms by which S. aureus induces osteomyelitis could therefore lead to a better understanding of the disease, its progression, and development of new treatments.Bone remodeling involves a continuous, coordinated equilibrium between bone synthesis and bone resorption, and two cell populations are responsible for the continual process (23). Osteoclasts drive the resorption of bone by acidification and release of lysosomal enzymes, while osteoblasts produce components of the bone matrix, principally type I collagen. Osteoblasts also produce factors which serve to modulate the ...

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Staphylococcus aureusInduces Expression of Receptor Activator of NF-κB Ligand and Prostaglandin E₂in Infected Murine Osteoblasts

et al. 2008

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“…PGs are produced in bone by many cells, especially osteoblasts (11,12), and production is stimulated by a variety of cytokines that are derived from macrophages or hematopoietic cells (13)(14)(15)(16)(17)(18). Several cytokines produced by marrow cells, such as IL-la, WL-1,6, IL-6, IL-11, and TNFa, have been implicated in the osteoporosis of estrogen deficiency (19)(20)(21)(22)(23)(24)(25)(26)(27).…”

Section: Introductionmentioning

confidence: 99%

Ovariectomy enhances and estrogen replacement inhibits the activity of bone marrow factors that stimulate prostaglandin production in cultured mouse calvariae.

Kawaguchi

Pilbeam²,

Vargas³

et al. 1995

J. Clin. Invest.

131

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To examine PG production in estrogen deficiency, we studied effects on cultured neonatal mouse calvariae of bone marrow supernatants (MSup) from sham-operated (SHAM), ovariectomized (OVX), or 1713-estradiol (OVX+E) -treated mice. MSups were obtained 3 wk after OVX when bone density had decreased significantly. 10-60% MSup increased medium PGE2 and levels of mRNA for inducible and constitutive prostaglandin G/H synthase (PGHS-2 and PGHS-1) and cytosolic phospholipase A2 in calvarial cultures. OVX MSups had twofold greater effects on PGHS-2 and medium PGE2 than other MSups. IL-1 receptor antagonist and anti-IL-la neutralizing antibody decreased MSup-stimulated PGHS-2 mRNA and PGE2 levels and diminished differences among OVX, sham-operated, and OVX+E groups. In contrast, antibodies to IL-18, IL-6, IL-li, and TNFa had little effect. There were no significant differences in IL-la concentrations or IL-la mRNA levels in MSups or marrow cells. PGHS-2 mRNA in freshly isolated tibiae from OVX mice was slightly greater than from sham-operated. We conclude that bone marrow factors can increase PG production through stimulation of PGHS-2; that OVX increases and estrogen decreases activity of these factors; and that IL-la activity, together with additional unknown factors, mediates the differential MSup effects. (J.

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“…It is known that PGE 2 is mainly produced by osteoblasts and acts as a potent stimulator of bone resorption (1)(2)(3). Inflammatory stimulants, such as IL-1 and IL-6, induce PGE 2 production by osteoblasts.…”

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Membrane-Bound Prostaglandin E Synthase-1-Mediated Prostaglandin E2 Production by Osteoblast Plays a Critical Role in Lipopolysaccharide-Induced Bone Loss Associated with Inflammation

Inada

Matsumoto

Uematsu

et al. 2006

The Journal of Immunology

116

141

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PGE2 acts as a potent stimulator of bone resorption in several disorders including osteoarthritis and periodontitis. Three PGE synthases (PGES) were isolated for PGE2 production, but which PGES has the major role in inflammatory bone resorption is still unclear. In this study, we examined the role of PGE2 in LPS-induced bone resorption using membrane-bound PGES (mPGES)-1-deficient mice (mPges1−/−). In osteoblasts from wild-type mice, PGE2 production was greatly stimulated by LPS following the expression of cyclooxygenase 2 and mPGES-1 mRNA, whereas no PGE2 production was found in osteoblasts from mPges1−/−. LPS administration reduced the bone volume in wild-type femur that was associated with an increased number of osteoclasts. In mPges1−/−, however, LPS-induced bone loss was reduced. We next examined whether mPGES-1 deficiency could alter the alveolar bone loss in LPS-induced experimental periodontitis. LPS was injected into the lower gingiva and bone mineral density of alveolar bone was measured. LPS induced the loss of alveolar bone in wild-type, but not in mPges1−/− mice, suggesting an mPGES-1 deficiency resistant to LPS-induced periodontal bone resorption. To understand the pathway of LPS-induced PGE2 production in osteoblast, we used C3H/HeJ mice with mutated tlr4. Osteoblasts from C3H/HeJ mice did not respond to LPS, and PGE2 production was not altered at all. LPS-induced bone loss in the femur was also impaired in C3H/HeJ mice. Thus, LPS binds to TLR4 on osteoblasts that directly induce mPGES-1 expression for PGE2 synthesis, leading to subsequent bone resorption. Therefore, mPGES-1 may provide a new target for the treatment of inflammatory bone disease.

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Stimulation of prostaglandin E2 and bone resorption by recombinant human interleukin 1 alpha in fetal mouse bones

Cited by 133 publications

References 14 publications

Staphylococcus aureusInduces Expression of Receptor Activator of NF-κB Ligand and Prostaglandin E₂in Infected Murine Osteoblasts

Staphylococcus aureusInduces Expression of Receptor Activator of NF-κB Ligand and Prostaglandin E₂in Infected Murine Osteoblasts

Ovariectomy enhances and estrogen replacement inhibits the activity of bone marrow factors that stimulate prostaglandin production in cultured mouse calvariae.

Membrane-Bound Prostaglandin E Synthase-1-Mediated Prostaglandin E2 Production by Osteoblast Plays a Critical Role in Lipopolysaccharide-Induced Bone Loss Associated with Inflammation

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Stimulation of prostaglandin E2 and bone resorption by recombinant human interleukin 1 alpha in fetal mouse bones

Cited by 133 publications

References 14 publications

Staphylococcus aureusInduces Expression of Receptor Activator of NF-κB Ligand and Prostaglandin E2in Infected Murine Osteoblasts

Staphylococcus aureusInduces Expression of Receptor Activator of NF-κB Ligand and Prostaglandin E2in Infected Murine Osteoblasts

Ovariectomy enhances and estrogen replacement inhibits the activity of bone marrow factors that stimulate prostaglandin production in cultured mouse calvariae.

Membrane-Bound Prostaglandin E Synthase-1-Mediated Prostaglandin E2 Production by Osteoblast Plays a Critical Role in Lipopolysaccharide-Induced Bone Loss Associated with Inflammation

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Staphylococcus aureusInduces Expression of Receptor Activator of NF-κB Ligand and Prostaglandin E₂in Infected Murine Osteoblasts

Staphylococcus aureusInduces Expression of Receptor Activator of NF-κB Ligand and Prostaglandin E₂in Infected Murine Osteoblasts