Gut microbiota and the periodontal disease: role of hyperhomocysteinemia

Periodontal disease is one of the most common conditions resulting from poor oral hygiene and is characterized by a destructive process in the periodontium that essentially includes gingiva, alveolar mucosa, cementum, periodontal ligament, and alveolar bone. Notably, the destructive event in the alveolar bone has been linked to homocysteine (Hcy) metabolism; however, it has not been fully investigated. Therefore; the implication of Hcy towards initiation, progression, and maintenance of the periodontal disease remains incompletely understood. Higher levels of Hcy (also known as hyperhomocysteinemia (HHcy)) exerts deleterious effects on gum health and teeth in distinct ways. Firstly, increased production of proinflammatory cytokines such as TNF-α, IL-1β, IL-6, and IL-8 leads to an inflammatory cascade of events that affect methionine (Met) and Hcy metabolism (i.e., 1-carbon metabolism) leading to HHcy. Secondly, metabolic dysregulation during chronic medical conditions increases systemic inflammation leading to a decrease in vitamins, more specifically B6, B12, and folic acid, that play important roles as cofactors in Hcy metabolism. Also, given the folate level in the HHcy state that is important during dysbiosis, these two conditions appear to be intimately related, and in this context, HHcy-induced dysbiosis may be one of the potential causes of periodontal disease. This paper sums up the link between periodontitis and HHcy, with a special emphasis on the “oral–gut microbiome axis” and the potential probiotic intervention towards warding off some of the serious periodontal disease conditions.

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Wnt Signaling in Periodontal Disease

Frontiers in Dental Medicine ◽

10.3389/fdmed.2021.763308 ◽

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.

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Is Inflammation a Friend or Foe for Orthodontic Treatment?: Inflammation in Orthodontically Induced Inflammatory Root Resorption and Accelerating Tooth Movement

International Journal of Molecular Sciences ◽

10.3390/ijms22052388 ◽

2021 ◽

Vol 22 (5) ◽

pp. 2388

Author(s):

Masaru Yamaguchi ◽

Shinichi Fukasawa

Keyword(s):

Inflammatory Mediators ◽

Orthodontic Treatment ◽

Alveolar Bone ◽

Tooth Movement ◽

Root Resorption ◽

Orthodontic Tooth Movement ◽

Tnf Α ◽

Orthodontic Forces ◽

Necrosis Factor

The aim of this paper is to provide a review on the role of inflammation in orthodontically induced inflammatory root resorption (OIIRR) and accelerating orthodontic tooth movement (AOTM) in orthodontic treatment. Orthodontic tooth movement (OTM) is stimulated by remodeling of the periodontal ligament (PDL) and alveolar bone. These remodeling activities and tooth displacement are involved in the occurrence of an inflammatory process in the periodontium, in response to orthodontic forces. Inflammatory mediators such as prostaglandins (PGs), interleukins (Ils; IL-1, -6, -17), the tumor necrosis factor (TNF)-α superfamily, and receptor activator of nuclear factor (RANK)/RANK ligand (RANKL)/osteoprotegerin (OPG) are increased in the PDL during OTM. OIIRR is one of the accidental symptoms, and inflammatory mediators have been detected in resorbed roots, PDL, and alveolar bone exposed to heavy orthodontic force. Therefore, these inflammatory mediators are involved with the occurrence of OIIRR during orthodontic tooth movement. On the contrary, regional accelerating phenomenon (RAP) occurs after fractures and surgery such as osteotomies or bone grafting, and bone healing is accelerated by increasing osteoclasts and osteoblasts. Recently, tooth movement after surgical procedures such as corticotomy, corticision, piezocision, and micro-osteoperforation might be accelerated by RAP, which increases the bone metabolism. Therefore, inflammation may be involved in accelerated OTM (AOTM). The knowledge of inflammation during orthodontic treatment could be used in preventing OIIRR and AOTM.

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

International Journal of Molecular Sciences ◽

10.3390/ijms22020695 ◽

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.

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Role of Zinc Transporter ZIP13 in Degenerative Changes in Periodontal Ligament and Alveolar Bone

Journal of Hard Tissue Biology ◽

10.2485/jhtb.25.49 ◽

2016 ◽

Vol 25 (1) ◽

pp. 49-56 ◽

Cited By ~ 2

Author(s):

Yayoi Idaira ◽

Takaaki Munemasa ◽

Toshiyuki Fukada ◽

Shinji Shimoda ◽

Yoshinobu Asada

Keyword(s):

Periodontal Ligament ◽

Alveolar Bone ◽

Zinc Transporter ◽

Degenerative Changes

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Telmisartan Prevents Alveolar Bone Loss by Decreasing the Expression of Osteoclasts Markers in Hypertensive Rats With Periodontal Disease

Frontiers in Pharmacology ◽

10.3389/fphar.2020.579926 ◽

2020 ◽

Vol 11 ◽

Author(s):

Victor Gustavo Balera Brito ◽

Mariana Sousa Patrocinio ◽

Maria Carolina Linjardi de Sousa ◽

Ayná Emanuelli Alves Barreto ◽

Sabrina Cruz Tfaile Frasnelli ◽

...

Keyword(s):

Angiotensin Ii ◽

Bone Loss ◽

Bone Formation ◽

Periodontal Disease ◽

Alveolar Bone ◽

Renin Angiotensin System ◽

Alveolar Bone Loss ◽

Hypertensive Rats ◽

Bone Formation Markers ◽

Tnf Α

Periodontal disease (PD) is a prevalent inflammatory disease with the most severe consequence being the loss of the alveolar bone and teeth. We therefore aimed to evaluate the effects of telmisartan (TELM), an angiotensin II type 1 receptor (Agtr1) antagonist, on the PD-induced alveolar bone loss, in Wistar (W) and Spontaneous Hypertensive Rats (SHRs). PD was induced by ligating the lower first molars with silk, and 10 mg/kg TELM was concomitantly administered for 15 days. The hemimandibles were subjected to microtomography, ELISA was used for detecting tumor necrosis factor (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), CXCL3, and CCL2, while qRT-PCR was used for analyzing expression of components of renin-angiotensin system (RAS) (Agt, Ace, Agt1r, Agt2r, Ace2, and Masr), and bone markers (Runx2, Osx, Catnb, Alp, Col1a1, Opn, Ocn, Bsp, Bmp2, Trap, Rank, Rankl, CtsK, Mmp-2, Mmp-9, and osteoclast-associated receptor (Oscar)). The SHR + PD group showed greater alveolar bone loss than the W + PD group, what was significantly inhibited by treatment with TELM, especially in the SHR group. Additionally, TELM reduced the production of TNF-α, IL-1β, and CXCL3 in the SHR group. The expression of Agt increased in the groups with PD, while Agtr2 reduced, and TELM reduced the expression of Agtr1 and increased the expression of Agtr2, in W and SHRs. PD did not induce major changes in the expression of bone formation markers, except for the expression of Alp, which decreased in the PD groups. The bone resorption markers expression, Mmp9, Ctsk, and Vtn, was higher in the SHR + PD group, compared to the respective control and W + PD group. However, TELM attenuated these changes and increased the expression of Runx2 and Alp. Our study suggested that TELM has a protective effect on the progression of PD, especially in hypertensive animals, as evaluated by the resorption of the lower alveolar bone. This can be partly explained by the modulation in the expression of Angiotensin II receptors (AT1R and AT2R), reduced production of inflammatory mediators, the reduced expression of resorption markers, and the increased expression of the bone formation markers.

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Role of Calprotectin as a Biomarker in Periodontal Disease

Mediators of Inflammation ◽

10.1155/2019/3515026 ◽

2019 ◽

Vol 2019 ◽

pp. 1-10 ◽

Cited By ~ 4

Author(s):

Lili Wei ◽

Mingwen Liu ◽

Haofei Xiong

Keyword(s):

Periodontal Disease ◽

Calcium Binding ◽

Alveolar Bone ◽

Inflammatory Diseases ◽

Periodontal Tissues ◽

Adaptive Immune ◽

S 100 ◽

And Function ◽

Plaque Biofilm

Periodontal disease (PD) is a common infectious and inflammatory disease characterised by inflammation of tissues surrounding and supporting the teeth and destruction of the associated alveolar bone, eventually resulting in tooth loss. This disease is caused by periodontopathic bacteria in plaque biofilm and resultant innate and adaptive immune responses in periodontal tissues. Calprotectin (CLP) is a calcium-binding protein of the S-100 protein family and is found to be induced by activated granulocytes, monocytes, and epithelial cells. CLP has been shown to play an important role in numerous inflammatory diseases and disorders. Increasing evidence indicates that CLP is involved in the progression of PD, and its levels may be associated with disease severity and outcome of periodontal treatments. This review will summarise recent studies regarding the presence, regulation, and function of CLP in PD. The findings indicate that CLP may be an effective biomarker for diagnosis and treatment for the PD.

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Role of PTH1R Signaling in Prx1+ Mesenchymal Progenitors during Eruption

Journal of Dental Research ◽

10.1177/0022034520934732 ◽

2020 ◽

Vol 99 (11) ◽

pp. 1296-1305

Author(s):

C. Cui ◽

R. Bi ◽

W. Liu ◽

S. Guan ◽

P. Li ◽

...

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Mesenchymal Stem Cells ◽

Bone Formation ◽

Bone Remodeling ◽

Periodontal Ligament ◽

Alveolar Bone ◽

Tooth Eruption ◽

Mesenchymal Progenitors

Tooth eruption is a complex process requiring precise interaction between teeth and adjacent tissues. Molecular analysis demonstrates that bone remodeling plays an essential role during eruption, suggesting that a parathyroid hormone 1 receptor (PTH1R) gene mutation is associated with disturbances in bone remodeling and results in primary failure of eruption (PFE). Recent research reveals the function of PTH1R signaling in mesenchymal progenitors, whereas the function of PTH1R in mesenchymal stem cells during tooth eruption remains incompletely understood. We investigated the specific role of PTH1R in Prx1+ progenitor expression during eruption. We found that Prx1+-progenitors occur in mesenchymal stem cells residing in alveolar bone marrow surrounding incisors, at the base of molars and in the dental follicle and pulp of incisors. Mice with conditional deletion of PTH1R using the Prx1 promoter exhibited arrested mandibular incisor eruption and delayed molar eruption. Micro–computed tomography, histomorphometry, and molecular analyses revealed that mutant mice had significantly reduced alveolar bone formation concomitant with downregulated gene expression of key regulators of osteogenesis in PTH1R-deficient cells. Moreover, culturing orofacial bone-marrow-derived mesenchymal stem cells (OMSCs) from Prx1Cre;PTH1Rfl/fl mice or from transfecting Cre recombinase adenovirus in OMSCs from PTH1Rfl/fl mice suggested that lack of Pth1r expression inhibited osteogenic differentiation in vitro. However, bone resorption was not affected by PTH1R ablation, indicating the observed reduced alveolar bone volume was mainly due to impaired bone formation. Furthermore, we found irregular periodontal ligaments and reduced Periostin expression in mutant incisors, implying loss of PTH1R results in aberrant differentiation of periodontal ligament cells. Collectively, these data suggest that PTH1R signaling in Prx1+ progenitors plays a critical role in alveolar bone formation and periodontal ligament development during eruption. These findings have implications for our understanding of the physiologic and pathologic function of PTH1R signaling in tooth eruption and the progression of PFE.

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Management of Periodontitis Associated with Endodontically Involved Teeth: A Case Series

The Journal of Contemporary Dental Practice ◽

10.5005/jcdp-6-2-118 ◽

2005 ◽

Vol 6 (2) ◽

pp. 118-129 ◽

Cited By ~ 1

Author(s):

Pradeep S. Anand ◽

K. Nandakumar

Keyword(s):

Oral Cavity ◽

Periodontal Disease ◽

Treatment Planning ◽

Dental Pulp ◽

Periodontal Ligament ◽

Alveolar Bone ◽

Case Series ◽

Disease Process ◽

Simultaneous Existence ◽

Treatment Procedures

Abstract The pulp and the periodontal attachment are the two components that enable a tooth to function in the oral cavity. Lesions of the periodontal ligament and adjacent alveolar bone may originate from infections of the periodontium or tissues of the dental pulp. The simultaneous existence of pulpal problems and inflammatory periodontal disease can complicate diagnosis and treatment planning. The function of the tooth is severely compromised when either one of these is involved in the disease process. Treatment of disease conditions involving both of these structures can be challenging and frequently requires combining both endodontic and periodontal treatment procedures. This article presents cases of periodontitis associated with endodontic lesions managed by both endodontic and periodontal therapy. Citation Anand PS, Nandakumar K. Management of Periodontitis Associated with Endodontically Involved Teeth: A Case Series. J Contemp Dent Pract 2005 May;(6)2:118-129.

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Mice lacking PLAP-1/asporin counteracts high fat diet-induced metabolic disorder and alveolar bone loss by controlling adipose tissue expansion

Scientific Reports ◽

10.1038/s41598-021-84512-2 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Hiromi Sakashita ◽

Satoru Yamada ◽

Masaki Kinoshita ◽

Tetsuhiro Kajikawa ◽

Tomoaki Iwayama ◽

...

Keyword(s):

Adipose Tissue ◽

Periodontal Disease ◽

Lipid Accumulation ◽

High Fat Diet ◽

Periodontal Ligament ◽

Metabolic Disorders ◽

Alveolar Bone ◽

High Fat ◽

Knock Out ◽

Knock Out Mice

AbstractAdipose tissue fibrosis with chronic inflammation is a hallmark of obesity-related metabolic disorders, and the role of proteoglycans in developing adipose tissue fibrosis is of interest. Periodontal disease is associated with obesity; however, the underlying molecular mechanisms remain unclear. Here we investigated the roles of periodontal ligament associated protein-1 (PLAP-1)/asporin, a proteoglycan preferentially and highly expressed in the periodontal ligament, in obesity-related adipose tissue dysfunction and adipocyte differentiation. It was found that PLAP-1 is also highly expressed in white adipose tissues. Plap-1 knock-out mice counteracted obesity and alveolar bone resorption induced by a high-fat diet. Plap-1 knock-down in 3T3-L1 cells resulted in less lipid accumulation, and recombinant PLAP-1 enhanced lipid accumulation in 3T3-L1 cells. In addition, it was found that primary preadipocytes isolated from Plap-1 knock-out mice showed lesser lipid accumulation than the wild-type (WT) mice. Furthermore, the stromal vascular fraction of Plap-1 knock-out mice showed different extracellular matrix gene expression patterns compared to WT. These findings demonstrate that PLAP-1 enhances adipogenesis and could be a key molecule in understanding the association between periodontal disease and obesity-related metabolic disorders.

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Periodontal Therapy in Dogs Using Bone Augmentation Products Marketed for Veterinary Use

Journal of the American Animal Hospital Association ◽

10.5326/jaaha-ms-6421 ◽

2017 ◽

Vol 53 (3) ◽

pp. 172-179

Author(s):

Molly Angel

Keyword(s):

Bone Loss ◽

Periodontal Disease ◽

Periodontal Ligament ◽

Bone Repair ◽

Alveolar Bone ◽

Clinical Symptoms ◽

Oral Examination ◽

Bone Augmentation ◽

Attachment Loss

ABSTRACT Periodontal disease is extremely common in companion animal practice. Patients presenting for a routine oral examination and prophylaxis may be found to have extensive periodontal disease and attachment loss. Vertical bone loss is a known sequela to periodontal disease and commonly involves the distal root of the mandibular first molar. This case report outlines two dogs presenting for oral examination and prophylaxis with general anesthesia. Both patients did not have any clinical symptoms of periodontal disease other than halitosis. Both patients were diagnosed with three-walled vertical bone loss defects of one or both mandibular first molars utilizing dental radiography as well as periodontal probing, measuring, and direct visual inspection. These defects were consistent with periodontal disease index stage 4 (>50% attachment loss). The lesions were treated with appropriate root planing and debridement. Bone augmentation products readily available and marketed for veterinary use were then utilized to fill the defects to promote both the re-establishment of normal alveolar bone height and periodontal ligament reattachment to the treated surface. Follow-up assessment and owner dedication is critical to treatment outcome. Both patients' 6 mo follow-up examinations radiographically indicated bone repair and replacement with visible periodontal ligament space.

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