Cannabidiol decreases bone resorption by inhibiting RANK/RANKL expression and pro-inflammatory cytokines during experimental periodontitis in rats

Abstract Staphylococcus aureus is a main pathogen of osteomyelitis and protein A is a virulence factor with high affinity for IgG. In this study, we investigated whether S. aureus affects the differentiation and bone resorption of osteoclasts through the IgG-binding capacity of protein A. Staphylococcus aureus pre-treated with serum or IgG showed marked enhancement in osteoclastogenesis and bone resorption compared to non-treated S. aureus or a protein A-deficient mutant. Blocking of the Fc receptor and deletion of the Fcγ receptor gene in osteoclast precursor cells showed that enhanced osteoclastogenesis stimulated by S. aureus IgG immune complexes (ICs) was mediated by the Fc receptor on osteoclast precursor cells. In addition, osteoclastogenesis stimulated by S. aureus ICs but not the protein A-deficient mutant was markedly reduced in osteoclast precursor cells of Myd88-knockout mice. Moreover, NFATc1, Syk and NF-κB signals were necessary for osteoclastogenesis stimulated by S. aureus ICs. The results suggest the contribution of a of Toll-like receptor 2 (TLR2)-Myd88 signal to the activity of S. aureus ICs. We further examined the expression of pro-inflammatory cytokines that is known to be enhanced by FcγR-TLR cross-talk. Osteoclasts induced by S. aureus ICs showed higher expression of TNF-α and IL-1β, and marked stimulation of proton secretion of osteoclasts activated by pro-inflammatory cytokines. Finally, injection of S. aureus, but not the protein A-deficient mutant, exacerbated bone loss in implantation and intra-peritoneal administration mouse models. Our results provide a novel mechanistic aspect of bone loss induced by S. aureus in which ICs and both Fc receptors and TLR pathways are involved.

Download Full-text

Effects of a Mikania laevigata extract on bone resorption and RANKL expression during experimental periodontitis in rats

Journal of Applied Oral Science ◽

10.1590/s1678-77572012000300008 ◽

2012 ◽

Vol 20 (3) ◽

pp. 340-346 ◽

Cited By ~ 7

Author(s):

Bruno B. Benatti ◽

Jozafá C. Campos-Júnior ◽

Vilmar J. Silva-Filho ◽

Polyanna M. Alves ◽

Isabela R. Rodrigues ◽

...

Keyword(s):

Bone Resorption ◽

Rankl Expression ◽

Experimental Periodontitis ◽

Mikania Laevigata

Download Full-text

IL-17 regulates expression of cytokines in human osteoblasts rather than bone-specific genes

Osteologie/Osteology ◽

10.1055/a-1177-5073 ◽

2020 ◽

Author(s):

Susanne Drynda ◽

Andreas Drynda ◽

Christoph H. Lohmann ◽

Jessica Bertrand ◽

Jörn Kekow

Keyword(s):

Bone Resorption ◽

Inflammatory Cytokines ◽

Osteoclast Differentiation ◽

Inflammatory Rheumatic Diseases ◽

Transcriptional Level ◽

Culture Model ◽

Tnf Α ◽

Primary Osteoblasts ◽

Pro Inflammatory Cytokines

Abstract Objective The cytokine IL-17 plays a crucial role in the development and promoting of inflammatory rheumatic diseases, such as psoriasis arthritis and ankylosing spondylitis. The influence of IL-17 on the osteoblast differentiation from mesenchymal stem cells has already been well studied. However, the effect of IL-17 on mature osteoblasts is not yet fully understood. Methods In this study, the influence of IL-17 on the expression of osteogenic markers and pro-inflammatory cytokines was analyzed on mRNA and protein level in an osteoblast cell culture model. Results Our data indicate that IL-17 alone has no significant influence on the expression of osteoblast-specific genes. However, a significant upregulation of pro-inflammatory cytokines at the transcriptional level by IL-17 was observed in primary osteoblasts. This effect on the regulation of pro-inflammatory cytokines was abolished completely by administration of a therapeutic anti-IL-17 antibody. Co-stimulation with TNF-α and IL-17 led to an upregulation of pro-inflammatory cytokines, which significantly exceeded the additive effect of both cytokines. In this co-stimulation, the anti-IL-17 antibody could not completely reverse the IL-17 effect. The same IL-17 and TNF-α effect was observed in osteoblast-like cells (MG63), whereas IL-17 alone did not induce the expression of pro-inflammatory cytokines. Conclusion The upregulation of the pro-inflammatory cytokines IL-1, IL-6, and IL-8 in primary osteoblasts by IL-17 indicates an indirect regulatory effect on osteoclastogenesis and activation of bone resorption. The therapeutic IL-17 antibody reduced the IL-17 induced release of pro-inflammatory cytokines by osteoblasts and this, in turn, could also reduce the effect on osteoclast differentiation and bone resorption. Our study underlines the important role of osteoblasts as major players in the osteoimmunologic network.

Download Full-text

Accelerated Alveolar Bone Loss in Mice Lacking Interleukin-10

Journal of Dental Research ◽

10.1177/154405910308200812 ◽

2003 ◽

Vol 82 (8) ◽

pp. 632-635 ◽

Cited By ~ 61

Author(s):

A. Al-Rasheed ◽

H. Scheerens ◽

D.M. Rennick ◽

H.M. Fletcher ◽

D.N. Tatakis

Keyword(s):

Bone Resorption ◽

Bone Loss ◽

Inflammatory Cytokines ◽

Alveolar Bone ◽

Interleukin 10 ◽

Alveolar Bone Loss ◽

Prevotella Intermedia ◽

Pro Inflammatory Cytokines

Interleukin-10 regulates pro-inflammatory cytokines, including those implicated in alveolar bone resorption. We hypothesized that lack of interleukin-10 leads to increased alveolar bone resorption. Male interleukin-10(−/−) mice, on 129/SvEv and C57BL/6J background, were compared with age-, sex-, and strain-matched interleukin-10(+/+) controls for alveolar bone loss. Immunoblotting was used for analysis of serum reactivity against bacteria associated with colitis and periodontitis. Interleukin-10(−/−) mice had significantly greater alveolar bone loss than interleukin-10(+/+) mice (p = 0.006). The 30–40% greater alveolar bone loss in interleukin-10(−/−) mice was evident in both strains, with C57BL/6J interleukin-10(−/−) mice exhibiting the most bone loss. Immunoblotting revealed distinct interleukin-10(−/−) serum reactivity against Bacteroides vulgatus, B. fragilis, Prevotella intermedia, and, to a lesser extent, against B. forsythus. The results of the present study suggest that lack of interleukin-10 leads to accelerated alveolar bone loss.

Download Full-text

Variation of the Cytokine Profiles in Gingival Crevicular Fluid Between Different Groups of Periodontally Healthy Teeth

Serbian Journal of Experimental and Clinical Research ◽

10.2478/sjecr-2019-0015 ◽

2019 ◽

Vol 0 (0) ◽

Author(s):

Ervin Taso ◽

Mia Rakic ◽

Vladimir Stefanovic ◽

Aleksandra Petković-Curcin ◽

Ivan Stanojevic ◽

...

Keyword(s):

Bone Resorption ◽

Inflammatory Cytokines ◽

Gingival Crevicular Fluid ◽

Posterior Teeth ◽

Periodontal Tissues ◽

Cytokine Profiles ◽

Anterior Teeth ◽

Cytokine Levels ◽

Crevicular Fluid ◽

Pro Inflammatory Cytokines

Abstract Profiling of biomarkers of physiological process represents an integrative part in optimisation of diagnostic markers in order to adjust the diagnostic ranges to the potential effects of the local factors such occlusal forces in case of periodontal tissues. The objective of this study was estimation of IL-1β, IL-2, IL-4, IL-5, IL-6, IL-9, IL-10, IL-12, IL-13, IL-17, IL-22, TNFα and IFNγ concentrations in gingival crevicular fluid samples (GCF) between different groups of teeth. Two hundred fifty-nine systemically healthy non-smokers having at least one vital tooth without restorations, with healthy periodontal tissues, were clinically examined and the GCF sample was retrieved. The cytokine levels were estimated using flow cytometry and compared between central incisors (CI), lateral incisors, canines, first premolars, second premo-lars, first molars and second molars. Cytokine profiles varied between different groups of teeth with tendency of increase in pro-inflammatory cytokines from anterior teeth toward molars. Molars might be considered teeth with natural predisposition for faster bone resorption while the adjustment of diagnostic range of periodontal biomarkers for anterior or posterior teeth should be considered within diagnostic context. Cytokine profiles varied between different groups of teeth with tendency of increase in pro-inflammatory cytokines from anterior teeth toward molars. Molars might be considered teeth with natural predisposition for faster bone resorption while the adjustment of diagnostic range of periodontal biomarkers for anterior or posterior teeth should be considered within diagnostic context.

Download Full-text

Effect of Paeonol on Tissue Destruction in Experimental Periodontitis of Rats

The American Journal of Chinese Medicine ◽

10.1142/s0192415x14500244 ◽

2014 ◽

Vol 42 (02) ◽

pp. 361-374 ◽

Cited By ~ 11

Author(s):

Chih-Yuan Chang ◽

Earl Fu ◽

Cheng-Yang Chiang ◽

Wei-Jeng Chang ◽

Wan-Chien Cheng ◽

...

Keyword(s):

Connective Tissue ◽

Inflammatory Cytokines ◽

Alveolar Bone ◽

Gingival Tissue ◽

Tartrate Resistant Acid Phosphatase ◽

Micro Ct ◽

Tissue Destruction ◽

Tissue Inflammation ◽

Experimental Periodontitis ◽

Pro Inflammatory Cytokines

We evaluated the effects of paeonol, a phenolic compound of Moutan Cortex, on the tissue inflammation and destruction in experimental periodontitis of rats. The maxillary palatal bony surfaces of 18 rats received injections of lipopolysaccharide (LPS, 5 mg/mL), PBS or LPS-plus-paeonol (40 mg/kg, intra-peritoneal injection) for three days. Five days later, the osteoclasts were examined and compared after tartrate-resistant acid phosphatase staining. In another 36 rats, the experimental periodontitis was induced by placing the ligatures around the maxillary second and mandibular first molars. Seven days later, the periodontal destruction and inflammation in rats with paeonol (40 mg/kg or 80 mg/kg) and those who had no ligature or without paeonol were compared by dental radiography, micro-computerized tomography (micro-CT), and histology. Gingival mRNA expressions of pre-inflammatory cytokines, including IL-1β' IL-6 and TNF-α were also examined. Compared to the effect of the LPS positive control, the paeonol injection significantly reduced the induced osteoclast formation. In ligature-induced periodontitis, the periodontal bone supporting ratio was significantly higher in the ligature-plus-paeonol groups compared to that of the ligature group, although they were still less than those in the non-ligature group. By micro-CT and by histology/histometry, a consistent anti-destructive effect was observed when paeonol was added. Moreover, less amount of inflammatory cell-infiltrated connective tissue area, connective tissue attachment, and mRNA expressions of pro-inflammatory cytokines were presented in the ligature-plus-paeonol groups than those in the ligature group. These results suggested that paeonol might have a protective potential on gingival tissue inflammation and alveolar bone loss during the process of periodontitis by inhibiting pro-inflammatory cytokines.

Download Full-text

Cytokine synergy, collagenases and cartilage collagen breakdown

Biochemical Society Symposium ◽

10.1042/bss0700125 ◽

2003 ◽

Vol 70 ◽

pp. 125-133 ◽

Cited By ~ 7

Author(s):

Tim E. Cawston ◽

Jenny M. Milner ◽

Jon B. Catterall ◽

Andrew D. Rowan

Keyword(s):

Matrix Metalloproteinases ◽

Inflammatory Cytokines ◽

Activator Protein 1 ◽

Activator Protein ◽

And Cartilage ◽

Pro Inflammatory Cytokines

We have investigated proteinases that degrade cartilage collagen. We show that pro-inflammatory cytokines act synergistically with oncastatin M to promote cartilage collagen resorption by the up-regulation and activation of matrix metalloproteinases (MMPs). The precise mechanisms are not known, but involve the up-regulation of c-fos, which binds to MMP promoters at a proximal activator protein-1 (AP-1) site. This markedly up-regulates transcription and leads to higher levels of active MMP proteins.

Download Full-text