Lipopolysaccharide-induced bone resorption is increased in TNF type 2 receptor-deficient mice in vivo

Mian, Anower Hussain; Saito, Hiroaki; Alles, Neil; Shimokawa, Hitoyata; Aoki, Kazuhiro; Ohya, Keiichi

doi:10.1007/s00774-007-0834-0

Cited by 18 publications

(20 citation statements)

References 34 publications

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“…1, an LPS‐induced inflammatory response was observed in WT and aly /+ control mice. This is consistent with a previous report showing that a single injection of 10 mg/kg of LPS is adequate to produce an inflammatory response and bone resorption in calvariae as well as long bones (8). Nuclear factor‐κB is responsible for the inflammatory bone resorption in many arthritis models (7,14,15).…”

Section: Discussionsupporting

confidence: 93%

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Defective nuclear factor-κB-inducing kinase in aly/aly mice prevents bone resorption induced by local injection of lipopolysaccharide

Soysa¹,

Alles²,

Takahashi³

et al. 2010

Journal of Periodontal Research

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Section: Discussionsupporting

confidence: 93%

“…Lipopolysaccharide induces bone resorption by increasing the formation and activity of osteoclasts (8). Histological sections of calvariae stained for TRAP revealed a blunted response to LPS‐induced osteoclastogenic stimuli in aly / aly mice.…”

Section: Resultsmentioning

confidence: 99%

Defective nuclear factor-κB-inducing kinase in aly/aly mice prevents bone resorption induced by local injection of lipopolysaccharide

Soysa¹,

Alles²,

Takahashi³

et al. 2010

Journal of Periodontal Research

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“…Calvariae and long bones from 8‐week‐old WT, aly / + , and aly / aly mice and 3‐week‐old WT, p100 −/+ , p100 −/− , p100 −/− relB −/+ , and p100 −/− relB −/− mice were embedded in mixtures of methyl methacrylate (MMA) and 2 hydroxyethyl methacrylate (GMA) resins as described elsewhere 11, 12. Coronal and sagittal sections (3 µm thick) from calvariae and long bones were prepared, respectively, as described elsewhere with minor modifications 13. Sections were stained with tartrate‐resistant acid phosphatase (TRAP) and counterstained with toluidine blue or methyl green.…”

Section: Methodsmentioning

confidence: 99%

The pivotal role of the alternative NF-κB pathway in maintenance of basal bone homeostasis and osteoclastogenesis

Soysa

Alles

Weih

et al. 2010

Journal of Bone and Mineral Research

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The alternative NF-kB pathway consists predominantly of NF-kB-inducing kinase (NIK), IkB kinase a (IKKa), p100/p52, and RelB. The hallmark of the alternative NF-kB signaling is the processing of p100 into p52 through NIK, thus allowing the binding of p52 and RelB. The physiologic relevance of alternative NF-kB activation in bone biology, however, is not well understood. To elucidate the role of the alternative pathway in bone homeostasis, we first analyzed alymphoplasic (aly/aly) mice, which have a defective NIK and are unable to process p100, resulting in the absence of p52. We observed increased bone mineral density (BMD) and bone volume, indicating an osteopetrotic phenotype. These mice also have a significant defect in RANKL-induced osteoclastogenesis in vitro and in vivo. NF-kB DNAbinding assays revealed reduced activity of RelA, RelB, and p50 and no binding activity of p52 in aly/aly osteoclast nuclear extracts after RANKL stimulation. To determine the role of p100 itself without the influence of a concomitant lack of p52, we used p100 À/À mice, which specifically lack the p100 inhibitor but still express p52. p100 À/À mice have an osteopenic phenotype owing to the increased osteoclast and decreased osteoblast numbers that was rescued by the deletion of one allele of the relB gene. Deletion of both allele of relB resulted in a significantly increased bone mass owing to decreased osteoclast activity and increased osteoblast numbers compared with wildtype (WT) controls, revealing a hitherto unknown role for RelB in bone formation. Our data suggest a pivotal role of the alternative NF-kB pathway, especially of the inhibitory role of p100, in both basal and stimulated osteoclastogenesis and the importance of RelB in both bone formation and resorption. ß

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“…Ten milligrams per kilogram of LPS or vehicle was injected subcutaneously into the calvariae under anesthesia on the day of tooth cutting. (27,28) …”

Section: Lps Injectionsmentioning

confidence: 99%

LPS-Induced Inhibition of Osteogenesis Is TNF-α Dependent in a Murine Tooth Extraction Model

Tomomatsu

Aoki

Alles

et al. 2009

Journal of Bone and Mineral Research

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TNF-a is a major etiologic factor of inflammatory bone diseases such as periodontitis and rheumatoid arthritis. In addition, patients with metabolic diseases such as chronic heart disease and diabetes have significantly increased plasma levels of TNF-a. Several lines of evidence show inhibition of osteoblastogenesis by TNF-a in vitro. Therefore, bone formation and osteogenesis in these patients might be inhibited because of TNF-a. However, little is known about the inhibitory role of TNF-a in bone formation/ osteogenesis in vivo. The purpose of this study was to investigate the role of TNF-a in osteogenesis using a murine tooth extraction model. Lipopolysaccharide (LPS) was injected subcutaneously into the calvariae of either wildtype (WT) or TNF-a-deficient (KO) mice. The left incisor was extracted 4 days after LPS injection. The measuring area was established as the tooth socket under the mesial root of the first molar. A significant increase in serum TNF-a levels after LPS injection was observed in WT mice. The BMD of the tooth socket was significantly decreased by LPS injection 21 days after extraction in WT but not in KO mice. Histomorphometric analysis showed a significant decrease in the mineral apposition rate after LPS injection, which appeared at an early stage in WT but not in KO mice. Injection of a peptide that blocked the TNF-a signaling pathway by preventing transmission of the NF-kB signal recovered the inhibition of osteogenesis observed after LPS injection. In conclusion, TNF-a might play a major role in LPS-induced inhibition of osteogenesis under inflammatory conditions.

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Lipopolysaccharide-induced bone resorption is increased in TNF type 2 receptor-deficient mice in vivo

Cited by 18 publications

References 34 publications

Defective nuclear factor-κB-inducing kinase in aly/aly mice prevents bone resorption induced by local injection of lipopolysaccharide

Defective nuclear factor-κB-inducing kinase in aly/aly mice prevents bone resorption induced by local injection of lipopolysaccharide

The pivotal role of the alternative NF-κB pathway in maintenance of basal bone homeostasis and osteoclastogenesis

LPS-Induced Inhibition of Osteogenesis Is TNF-α Dependent in a Murine Tooth Extraction Model

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