scholarly journals Elevated Expression of Cathepsin K in Periodontal Ligament Fibroblast by Inflammatory Cytokines Accelerates Osteoclastogenesis via Paracrine Mechanism in Periodontal Disease

2021 ◽  
Vol 22 (2) ◽  
pp. 695
Author(s):  
Soon Chul Heo ◽  
Yu Na Kim ◽  
YunJeong Choi ◽  
Ji-Young Joo ◽  
Jae Joon Hwang ◽  
...  
Keyword(s):  
Periodontal Disease ◽  
Inflammatory Cytokines ◽  
Periodontal Ligament ◽  
Cathepsin K ◽  
Periodontal Ligament Fibroblasts ◽  
Supporting Cells ◽  
Inflammatory Conditions ◽  
Elevated Expression ◽  
Macrophage Colony

Cathepsin K (CTSK) is a cysteine protease that is mainly produced from mature osteoclasts and contributes to the destruction of connective tissues and mineralized matrix as a consequence of periodontal disease (PD). However, few studies have reported its regulatory role in osteoclastogenesis-supporting cells in inflammatory conditions. Here, we investigated the role of CTSK in osteoclastogenesis-supporting cells, focusing on the modulation of paracrine function. Microarray data showed that CTSK was upregulated in PD patients compared with healthy individuals, which was further supported by immunohistochemistry and qPCR analyses performed with human gingival tissues. The expression of CTSK in the osteoclastogenesis-supporting cells, including dental pulp stem cells, gingival fibroblasts, and periodontal ligament fibroblasts (PDLFs) was significantly elevated by treatment with inflammatory cytokines such as TNFα and IL-1β. Moreover, TNFα stimulation potentiated the PDLF-mediated osteoclastogenesis of bone marrow-derived macrophages. Interestingly, small interfering RNA-mediated silencing of CTSK in PDLF noticeably attenuated the TNFα-triggered upregulation of receptor activator of nuclear factor kappa-B ligand (RANKL), macrophage colony-stimulating factor, and RANKL/osteoprotegerin ratio, thereby abrogating the enhanced osteoclastogenesis-supporting activity of PDLF. Collectively, these results suggest a novel role of CTSK in the paracrine function of osteoclastogenesis-supporting cells in periodontal disease.

scholarly journals Myeloid HIF1α Is Involved in the Extent of Orthodontically Induced Tooth Movement

Biomedicines ◽  
2021 ◽  
Vol 9 (7) ◽  
pp. 796
Author(s):  
Christian Kirschneck ◽  
Nadine Straßmair ◽  
Fabian Cieplik ◽  
Eva Paddenberg ◽  
Jonathan Jantsch ◽  
...  
Keyword(s):  
Bone Density ◽  
Periodontal Ligament ◽  
Tooth Movement ◽  
Hypoxia Inducible Factor ◽  
Myeloid Cells ◽  
Orthodontic Tooth Movement ◽  
Periodontal Ligament Fibroblasts ◽  
Expression Of Genes ◽  
Periodontal Bone Loss

During orthodontic tooth movement, transcription factor hypoxia-inducible factor 1α (HIF1α) is stabilised in the periodontal ligament. While HIF1α in periodontal ligament fibroblasts can be stabilised by mechanical compression, in macrophages pressure application alone is not sufficient to stabilise HIF1α. The present study was conducted to investigate the role of myeloid HIF1α during orthodontic tooth movement. Orthodontic tooth movement was performed in wildtype and Hif1αΔmyel mice lacking HIF1α expression in myeloid cells. Subsequently, µCT images were obtained to determine periodontal bone loss, extent of orthodontic tooth movement and bone density. RNA was isolated from the periodontal ligament of the control side and the orthodontically treated side, and the expression of genes involved in bone remodelling was investigated. The extent of tooth movement was increased in Hif1αΔmyel mice. This may be due to the lower bone density of the Hif1αΔmyel mice. Deletion of myeloid Hif1α was associated with increased expression of Ctsk and Acp5, while both Rankl and its decoy receptor Opg were increased. HIF1α from myeloid cells thus appears to play a regulatory role in orthodontic tooth movement.

scholarly journals The role of 25-hydroxyvitamin-D3 and vitamin D receptor gene in human periodontal ligament fibroblasts as response to orthodontic compressive strain: an in vitro study

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Erika Calvano Küchler ◽  
Agnes Schröder ◽  
Vinicius Broska Teodoro ◽  
Ute Nazet ◽  
Rafaela Scariot ◽  
...  
Keyword(s):  
Gene Expression ◽  
Vitamin D ◽  
Single Nucleotide Polymorphisms ◽  
Periodontal Ligament ◽  
Compressive Strain ◽  
Nucleotide Polymorphisms ◽  
Periodontal Ligament Fibroblasts ◽  
Single Nucleotide ◽  
Cox 2

Abstract Background This study aimed to investigate, if different physiological concentrations of vitamin D (25(OH)D3) and single nucleotide polymorphisms in vitamin D receptor (VDR) gene have an impact on gene expression in human periodontal ligament (hPDL) fibroblasts induced by simulated orthodontic compressive strain. Methods A pool of hPDL fibroblasts was treated in absence or presence of 25(OH)D3 in 3 different concentrations (10, 40 and 60 ng/ml). In order to evaluate the role of single nucleotide polymorphisms in the VDR gene, hPDL fibroblasts from 9 patients were used and treated in absence or presence of 40 ng/ml 25(OH)D3. Each experiment was performed with and without simulated orthodontic compressive strain. Real-time PCR was used for gene expression and allelic discrimination analysis. Relative expression of dehydrocholesterol reductase (DHCR7), Sec23 homolog A, amidohydrolase domain containing 1 (AMDHD1), vitamin D 25-hydroxylase (CYP2R1), Hydroxyvitamin D-1-α hydroxylase, receptor activator of nuclear factor-κB ligand (RANKL), osteoprotegerin (OPG), cyclooxygenase-2 (COX-2) and interleukin-6 (IL6) was assessed. Three single nucleotide polymorphisms in VDR were genotyped. Parametric or non-parametric tests were used with an alpha of 5%. Results RANKL, RANKL:OPG ratio, COX-2, IL-6, DHCR7, CYP2R1 and AMDHD1 were differentially expressed during simulated orthodontic compressive strain (p < 0.05). The RANKL:OPG ratio was downregulated by all concentrations (10 ng/ml, 40 ng/ml and 60 ng/ml) of 25(OH)D3 (mean = 0.96 ± 0.68, mean = 1.61 ± 0.66 and mean = 1.86 ± 0.78, respectively) in comparison to the control (mean 2.58 ± 1.16) (p < 0.05). CYP2R1 gene expression was statistically modulated by the different 25(OH)D3 concentrations applied (p = 0.008). Samples from individuals carrying the GG genotype in rs739837 presented lower VDR mRNA expression and samples from individuals carrying the CC genotype in rs7975232 presented higher VDR mRNA expression (p < 0.05). Conclusions Simulated orthodontic compressive strain and physiological concentrations of 25(OH)D3 seem to regulate the expression of orthodontic tooth movement and vitamin-D-related genes in periodontal ligament fibroblasts in the context of orthodontic compressive strain. Our study also suggests that single nucleotide polymorphisms in the VDR gene regulate VDR expression in periodontal ligament fibroblasts in the context of orthodontic compressive strain.

scholarly journals The role of intestinal microbiota in the pathophysiology of depression

2018 ◽  
Vol 72 ◽  
pp. 795-805
Author(s):  
Apolonia Stefaniak ◽  
Karolina Janion ◽  
Beata Stanuch
Keyword(s):  
Inflammatory Cytokines ◽  
Intestinal Microbiota ◽  
Pharmacological Therapy ◽  
World Health ◽  
Cell Mediated Immunity ◽  
Inflammatory Conditions ◽  
Current State ◽  
High Prevalence ◽  
Health Organization

Depression is a mental disorder with a high prevalence. According to World Health Organization, it is a frequent cause of disability and the leading cause of suicide, with its risk increasing with age. The disorder is commonly diagnosed in patients with acute or chronic inflammatory conditions. Depression is typically accompanied by weakened T cell-mediated immunity, as well as abnormal secretion of pro- and anti-inflammatory cytokines and the resulting imbalance between them. The current developments in the field include a link established between depression and changes in intestinal microflora, suggested by numerous trials involving animals and also a small number of studies conducted on people. This paper is a review of the publications regarding the role of intestinal microbiota in the pathophysiology of depression found in PubMed and Web of Science repositories. The results of studies published over the last decade confirm the significance of intestinal microbiota for the pathophysiology of depression. One of the ways in which intestinal microbiota may impact the development of depression is the response of the innate immunity system to bacterial lipopolysaccharide (LPS), resulting with the stimulation of pro-inflammatory cytokines. The modifications of gut microflora have also been linked to changes in the hypothalamic- pituitary-adrenal axis, in the metabolism of tryptophan, (which is a serotonin substrate) and in neurotransmitter levels in the brain. Even though the results cited in this review seem promising, our current state of knowledge in this respect remains far from satisfactory, warranting further investigation into the potential of bacteria for supplementing the pharmacological therapy of depression.

scholarly journals Role of intracellular Ca 2+ –based mechanotransduction of human periodontal ligament fibroblasts

2019 ◽  
Vol 33 (9) ◽  
pp. 10409-10424 ◽  
Author(s):  
Ei Ei Hsu Hlaing ◽  
Yoshihito Ishihara ◽  
Ziyi Wang ◽  
Naoya Odagaki ◽  
Hiroshi Kamioka
Keyword(s):  
Periodontal Ligament ◽  
Periodontal Ligament Fibroblasts ◽  
Intracellular Ca ◽  
Human Periodontal Ligament Fibroblasts

scholarly journals Enhancement of Anti-Inflammatory and Osteogenic Abilities of Mesenchymal Stem Cells via Cell-to-Cell Adhesion to Periodontal Ligament-Derived Fibroblasts

2017 ◽  
Vol 2017 ◽  
pp. 1-12 ◽  
Author(s):  
Keita Suzuki ◽  
Naoyuki Chosa ◽  
Shunsuke Sawada ◽  
Naoki Takizawa ◽  
Takashi Yaegashi ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Inflammatory Cytokines ◽  
Periodontal Ligament ◽  
Direct Contact ◽  
Cell Types ◽  
Stem Cell Markers ◽  
Periodontal Ligament Fibroblasts ◽  
Anti Inflammatory ◽  
Inflammatory Tissue

Mesenchymal stem cells (MSCs) are involved in anti-inflammatory events and tissue repair; these functions are activated by their migration or homing to inflammatory tissues in response to various chemokines. However, the mechanism by which MSCs interact with other cell types in inflammatory tissue remains unclear. We investigated the role of periodontal ligament fibroblasts (PDL-Fs) in regulating the anti-inflammatory and osteogenic abilities of bone marrow-derived- (BM-) MSCs. The expression of monocyte chemotactic protein- (MCP-)1 was significantly enhanced by stimulation of PDL-Fs with inflammatory cytokines. MCP-1 induced the migratory ability of BM-MSCs but not PDL-Fs. Expression levels of anti-inflammatory and inflammatory cytokines were increased and decreased, respectively, by direct-contact coculture between MSCs and PDL-Fs. In addition, the direct-contact coculture enhanced the expression of MSC markers that play important roles in the self-renewal and maintenance of multipotency of MSCs, which in turn induced the osteogenic ability of the cells. These results suggest that MCP-1 induces the migration and homing of BM-MSCs into the PDL inflammatory tissue. The subsequent adherence of MSCs to PDL-Fs plays an immunomodulatory role to terminate inflammation during wound healing and upregulates the expression stem cell markers to enhance the stemness of MSCs, thereby facilitating bone formation in damaged PDL tissue.

scholarly journals Wnt Signaling in Periodontal Disease

2021 ◽  
Vol 2 ◽  
Author(s):  
David González-Quintanilla ◽  
Nicolás Abásolo ◽  
Pablo Astudillo
Keyword(s):  
Periodontal Disease ◽  
Wnt Signaling ◽  
Periodontal Ligament ◽  
Chronic Condition ◽  
Wnt Pathway ◽  
Alveolar Bone ◽  
Canonical Pathways ◽  
Canonical Wnt ◽  
Proper Balance

Periodontitis is a multifactorial and chronic condition associated with the formation of a dysbiotic biofilm, leading to a pro-inflammatory environment that can modulate cell signaling. The Wnt pathway plays fundamental roles during homeostasis and disease, and emerging evidence suggests its involvement in the maintenance of the periodontium and the development of periodontitis. Here, we summarize the role of the Wnt/β-catenin and non-canonical Wnt signaling pathways in periodontitis. The accumulated data suggests specific roles for each branch of the Wnt pathway. Wnt5a emerges as a critical player promoting periodontal ligament remodeling and impairing regenerative responses modulated by the Wnt/β-catenin pathway, such as alveolar bone formation. Collectively, the evidence suggests that achieving a proper balance between the Wnt/β-catenin and non-canonical pathways, rather than their independent modulation, might contribute to controlling the progression and severity of the periodontal disease.

scholarly journals Fisetin inhibits inflammation and induces autophagy by mediating PI3K/AKT/mTOR signaling in LPS-induced RAW264.7 cells

2021 ◽  
Author(s):  
Yue Sun ◽  
Hong Qin ◽  
Huihui Zhang ◽  
Xiangling Feng ◽  
Lina Yang ◽  
...  
Keyword(s):  
Inflammatory Cytokines ◽  
Immunofluorescence Assay ◽  
Mtor Signaling ◽  
Raw264.7 Cells ◽  
System Response ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Inflammatory Mechanism ◽  
Elevated Expression

Background: Fisetin, a natural potent flavonoid, has various beneficial, pharmacological activities. In this study, we investigated expression changes of the fisetin regulating genes in lipopolysaccharide (LPS)-treated RAW264.7 cells and explored the role of fisetin in inflammation and autophagy. Methods and results: Microarray analysis identified 1,071 genes that were regulated by fisetin in LPS-treated RAW264.7 cells, and these genes were mainly related to the process of immune system response. Quantitative real-time polymerase chain reaction and Bio-Plex analysis indicated that fisetin decreased the expression and secretion of several inflammatory cytokines in cells administered with LPS. Western blot analysis and immunofluorescence assay showed that fisetin decreased microtubule-associated protein 1 light-chain 3B (LC3B) and lysosome-associated membrane protein 1 (LAMP1) expression in LPS-treated cells, while the autophagy inhibitor chloroquine (CQ) could partially reverse this effect. In addition, fisetin reduced the elevated expression of p-PI3K, p-AKT and p-mTOR induced by LPS in a concentration-dependent manner. Conclusions: Fisetin diminished the expression and secretion of inflammatory cytokines and facilitated autophagosome- lysosome fusion and degradation in LPS-treated RAW264.7 cells via inhibition of the PI3K/ AKT/mTOR signaling pathway. Overall, the results of this study provide new clues for the anti-inflammatory mechanism of fisetin and explain the crosstalk between autophagy and inflammation to some extent.

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