Macrophage Activation Results in Bone Resorption

Lassus, Jan; Salo, Jari; Jiranek, William A.; Santavirta, Seppo; Nevalainen, Juha; Matucci‐Cerinic, Marco; Horák, Pavel; Konttinen, Yrjö T.

doi:10.1097/00003086-199807000-00003

Cited by 96 publications

(88 citation statements)

References 44 publications

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“…The significant decrease in alveolar bone resorption by clodronate liposome treatment indicates that macrophages play an important role in mediating bone resorption in the mouse periodontitis model. This finding is consistent with previous studies indicating that macrophages have a role in osteoclast development and differentiation, as well as in helping to provide sites for osteoclast attachment and bone resorption (34)(35)(36)38).…”

Section: Discussionsupporting

confidence: 93%

“…During bone resorption, macrophages are required to degrade the organic bone matrix, thus providing the attachment sites and chemotactic factors for osteoclasts (36,37). Once the osteoclasts attach to the degraded bone matrix, they form multinucleated cells and begin to resorb bone (38).…”

Section: Discussionmentioning

confidence: 99%

“…Macrophages are a major source of chemokines, including MIP-1a and IL-8, which are involved in the migration and activation of phagocytic cells and lymphocytes during inflammatory responses (31)(32)(33). In addition, macrophage lineages are recognized as precursors to osteoclasts, the primary cells responsible for bone resorption (34)(35)(36). The macrophage is considered essential for the degradation of organic bone matrix, providing attachment sites for osteoclasts that differentiate to form multinucleated cells and resorb bone (36)(37)(38).…”

mentioning

confidence: 99%

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Macrophage Depletion Abates Porphyromonas gingivalis–Induced Alveolar Bone Resorption in Mice

Lam

O'Brien-Simpson

Lenzo

et al. 2014

The Journal of Immunology

114

140

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The role of the macrophage in the immunopathology of periodontitis has not been well defined. In this study, we show that intraoral inoculation of mice with Porphyromonas gingivalis resulted in infection, alveolar bone resorption, and a significant increase in F4/80+ macrophages in gingival and submandibular lymph node tissues. Macrophage depletion using clodronate-liposomes resulted in a significant reduction in F4/80+ macrophage infiltration of gingival and submandibular lymph node tissues and significantly (p < 0.01) less P. gingivalis–induced bone resorption compared with controls in BALB/c and C57BL/6 mice. In both mouse strains, the P. gingivalis–specific IgG Ab subclass and serum cytokine [IL-4, IL-10, IFN-γ, and IL-12 (p70)] responses were significantly (p < 0.01) lower in the macrophage-depleted groups. Macrophage depletion resulted in a significant reduction in the level of P. gingivalis infection, and the level of P. gingivalis infection was significantly correlated with the level of alveolar bone resorption. M1 macrophages (CD86+), rather than M2 macrophages (CD206+), were the dominant macrophage phenotype of the gingival infiltrate in response to P. gingivalis infection. P. gingivalis induced a significant (p < 0.01) increase in NO production and a small increase in urea concentration, as well as a significant increase in the secretion of IL-1β, IL-6, IL-10, IL-12 (p70), eotaxin, G-CSF, GM-CSF, macrophage chemoattractant protein-1, macrophage inflammatory protein-α and -β, and TNF-α in isolated murine macrophages. In conclusion, P. gingivalis infection induced infiltration of functional/inflammatory M1 macrophages into gingival tissue and alveolar bone resorption. Macrophage depletion reduced P. gingivalis infection and alveolar bone resorption by modulating the host immune response.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

Macrophage Depletion Abates Porphyromonas gingivalis–Induced Alveolar Bone Resorption in Mice

Lam

O'Brien-Simpson

Lenzo

et al. 2014

The Journal of Immunology

114

140

View full text Add to dashboard Cite

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“…(TNFa) are potent mediators of bone resorption, [14][15][16][17][18] and recently, the immune-activating cytokines PDGF and IL-11 have also been identified within the periprosthetic tissue. 19,20 These cytokines provide activation signals to lymphocytes, 21 and in turn, the lymphocyte-derived cytokines interleukin 2 (IL-2), interleukin 6 (IL-6) and gamma interferon (IFN-g) may influence osteoclastic activity and bone remodeling.…”

Section: Pathogenesis Of Aseptic Looseningmentioning

confidence: 99%

Aseptic loosening

2004

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“…This wear debris stimulates local macrophage and fibroblast recruitment and release of pro-inflammatory cytokines, including interleukin-1 (IL-1), IL-6, IL-18, and tumor necrosis factor (TNF), that alter the balance of osteoclast and osteoblast activity in favor of bone resorption. 1,2 Anti-inflammatory cytokines, including IL-1 receptor antagonist (IL-1Ra) and IL-10, are also produced by activated macrophages in osteolysis and act to down-regulate the production of pro-inflammatory cytokines and inhibit osteoclastogenesis. 3,4 However, the net effect of wear debris particles on the balance of pro-versus anti-inflammatory cytokines in clinical populations, and their association with susceptibility to osteolysis, are unknown.…”

mentioning

confidence: 99%

Individual susceptibility to periprosthetic osteolysis is associated with altered patterns of innate immune gene expression in response to pro‐inflammatory stimuli

Gordon

Greenfield

Eastell

et al. 2010

Journal Orthopaedic Research

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Susceptibility to osteolysis after total hip arthroplasty (THA) varies between individuals. We examined whether patients susceptible to osteolysis (group I, n ¼ 34 subjects) after cemented Charnley THA have quantitatively different innate immune responses to pro-inflammatory stimuli versus patients without this susceptibility (group II, n ¼ 28 subjects) at a mean of 14 years after primary surgery. Extracted peripheral blood mononuclear cells were stimulated for 3 h using endotoxin (lipopolysaccharide-LPS, 100 ng/mL), endotoxinstripped titanium particles (Ti) or endotoxin-stripped particles with adherent LPS added-back (TI þ LPS). Subjects returned 1 week later and the experimental protocol was repeated. Assays for mRNA induction for interleukin (IL)-1a, IL-1b, IL-1Ra, IL-6, IL-10, IL-18, and tumor necrosis factor (TNF) were made using quantitative real-time PCR. Although baseline levels of mRNA expression were slightly lower in group I, inducibility of mRNA expression was markedly greater in group I versus group II for all cytokines in response to LPS or Ti þ LPS, and for IL-1a in response to Ti (P < 0.05). LPS or Ti þ LPS stimulation also resulted in an increase in the IL-1/IL-1Ra mRNA ratio in group I versus group II (P < 0.05). mRNA induction was highly reproducible between subject visits (r > 0.7, P < 0.001). Osteolysis-susceptible patients show repeatable, quantitatively different patterns of innate cytokine gene expression in response to pro-inflammatory stimuli versus THA patients who do not display this susceptibility. These innate immune differences may contribute to the variation in osteolysis-susceptibility observed clinically between individuals. ß

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Macrophage Activation Results in Bone Resorption

Cited by 96 publications

References 44 publications

Macrophage Depletion Abates Porphyromonas gingivalis–Induced Alveolar Bone Resorption in Mice

Macrophage Depletion Abates Porphyromonas gingivalis–Induced Alveolar Bone Resorption in Mice

Aseptic loosening

Individual susceptibility to periprosthetic osteolysis is associated with altered patterns of innate immune gene expression in response to pro‐inflammatory stimuli

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