Department of Periodontology

Permanent URI for this community

https://hdl.handle.net/1805/6755

Browse

Browsing Department of Periodontology by Author "AlQallaf, Hawra"

Now showing 1 - 3 of 3
  • Thumbnail Image
    Item
    Differential profiles of soluble and cellular toll like receptor (TLR)-2 and 4 in chronic periodontitis
    (PLOS, 2018-12-20) AlQallaf, Hawra; Hamada, Yusuke; Blanchard, Steven; Shin, Daniel; Gregory, Richard; Srinivasan, Mythily; Periodontology, School of Dentistry
    Chronic periodontitis is a common inflammatory disease initiated by a complex microbial biofilm and mediated by the host response causing destruction of the supporting tissues of the teeth. Host recognition of pathogens is mediated by toll-like receptors (TLRs) that bind conserved molecular patterns shared by large groups of microorganisms. The oral epithelial cells respond to most periodontopathic bacteria via TLR-2 and TLR-4. In addition to the membrane-associated receptors, soluble forms of TLR-2 (sTLR-2) and TLR-4 (sTLR-4) have been identified and are thought to play a regulatory role by binding microbial ligands. sTLR-2 has been shown to arise from ectodomain shedding of the extracellular domain of the membrane receptor and sTLR-4 is thought to be an alternate spliced form. Many studies have previously reported the presence of elevated numbers of viable exfoliated epithelial cells in the saliva of patients with chronic periodontitis. The objective of this study was to investigate the potential value of salivary sTLR-2 and sTLR-4 together with the paired epithelial cell-associated TLR-2/4 mRNA as diagnostic markers for chronic periodontitis. Unstimulated whole saliva was collected after obtaining informed consent from 40 individuals with either periodontitis or gingivitis. The sTLR-2 and sTLR4 in saliva was measured by enzyme-linked immunosorbent assay. The TLR-2 and TLR-4 transcript in the epithelial cells in saliva was measured by real time polymerase chain reaction. While levels of sTLR-2 exhibited an inverse correlation, sTLR-4 positively correlated with clinical parameters in the gingivitis cohort. Interestingly, both correlations were lost in the periodontitis cohort indicating a dysregulated host response. On the other hand, while the sTLR-2 and the paired epithelial cell associated TLR-2 mRNA exhibited a direct correlation (r2 = 0.62), that of sTLR4 and TLR-4 mRNA exhibited an inverse correlation (r2 = 0.53) in the periodontitis cohort. Collectively, assessments of salivary sTLR2 and sTLR4 together with the respective transcripts in the epithelial cells could provide clinically relevant markers of disease progression from gingivitis to periodontitis.
  • Thumbnail Image
    Item
    Differential profiles of soluble and cellular toll like receptor (TLR)-2 and 4 in chronic periodontitis
    (PLOS, 2018-12-20) AlQallaf, Hawra; Hamada, Yusuke; Blanchard, Steven; Shin, Daniel; Gregory, Richard; Srinivasan, Mythily; Periodontology, School of Dentistry
    Chronic periodontitis is a common inflammatory disease initiated by a complex microbial biofilm and mediated by the host response causing destruction of the supporting tissues of the teeth. Host recognition of pathogens is mediated by toll-like receptors (TLRs) that bind conserved molecular patterns shared by large groups of microorganisms. The oral epithelial cells respond to most periodontopathic bacteria via TLR-2 and TLR-4. In addition to the membrane-associated receptors, soluble forms of TLR-2 (sTLR-2) and TLR-4 (sTLR-4) have been identified and are thought to play a regulatory role by binding microbial ligands. sTLR-2 has been shown to arise from ectodomain shedding of the extracellular domain of the membrane receptor and sTLR-4 is thought to be an alternate spliced form. Many studies have previously reported the presence of elevated numbers of viable exfoliated epithelial cells in the saliva of patients with chronic periodontitis. The objective of this study was to investigate the potential value of salivary sTLR-2 and sTLR-4 together with the paired epithelial cell-associated TLR-2/4 mRNA as diagnostic markers for chronic periodontitis. Unstimulated whole saliva was collected after obtaining informed consent from 40 individuals with either periodontitis or gingivitis. The sTLR-2 and sTLR4 in saliva was measured by enzyme-linked immunosorbent assay. The TLR-2 and TLR-4 transcript in the epithelial cells in saliva was measured by real time polymerase chain reaction. While levels of sTLR-2 exhibited an inverse correlation, sTLR-4 positively correlated with clinical parameters in the gingivitis cohort. Interestingly, both correlations were lost in the periodontitis cohort indicating a dysregulated host response. On the other hand, while the sTLR-2 and the paired epithelial cell associated TLR-2 mRNA exhibited a direct correlation (r2 = 0.62), that of sTLR4 and TLR-4 mRNA exhibited an inverse correlation (r2 = 0.53) in the periodontitis cohort. Collectively, assessments of salivary sTLR2 and sTLR4 together with the respective transcripts in the epithelial cells could provide clinically relevant markers of disease progression from gingivitis to periodontitis.
  • Thumbnail Image
    Item
    Effects of IL-34 and anti-IL-34 neutralizing mAb on alveolar bone loss in a ligature-induced model of periodontitis
    (Wiley, 2023-10-30) Duarte, Carolina; Yamada, Chiaki; Ngala, Bidii; Garcia, Christopher; Akkaoui, Juliet; Birsa, Maxim; Ho, Anny; Nusbaum, Amilia; AlQallaf, Hawra; John, Vanchit; Movila, Alexandru; Periodontology, School of Dentistry
    Macrophage colony-stimulating factor (M-CSF) and interleukin-34 (IL-34) are ligands for the colony-stimulating factor-1 receptor (CSF-1r) expressed on the surface of monocyte/macrophage lineage cells. The importance of coordinated signaling between M-CSF/receptor activator of the nuclear factor kappa-Β ligand (RANKL) in physiological and pathological bone remodeling and alveolar bone loss in response to oral bacterial colonization is well established. However, our knowledge about the IL-34/RANKL signaling in periodontal bone loss remains limited. Recently published cohort studies have demonstrated that the expression patterns of IL-34 are dramatically elevated in gingival crevicular fluid collected from patients with periodontitis. Therefore, the present study aims to evaluate the effects of IL-34 on osteoclastogenesis in vitro and in experimental ligature-mediated model of periodontitis using male mice. Our initial in vitro study demonstrated increased RANKL-induced osteoclastogenesis of IL-34-primed osteoclast precursors (OCPs) compared to M-CSF-primed OCPs. Using an experimental model of ligature-mediated periodontitis, we further demonstrated elevated expression of IL-34 in periodontal lesions. In contrast, M-CSF levels were dramatically reduced in these periodontal lesions. Furthermore, local injections of mouse recombinant IL-34 protein significantly elevated cathepsin K activity, increased the number of tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts and promoted alveolar bone loss in periodontitis lesions. In contrast, anti-IL-34 neutralizing monoclonal antibody significantly reduced the level of alveolar bone loss and the number of TRAP-positive osteoclasts in periodontitis lesions. No beneficial effects of locally injected anti-M-CSF neutralizing antibody were observed in periodontal lesions. This study illustrates the role of IL-34 in promoting alveolar bone loss in periodontal lesions and proposes the potential of anti-IL34 monoclonal antibody (mAb)-based therapeutic regimens to suppress alveolar bone loss in periodontitis lesions.