scholarly journals Diabetes Medication Metformin Inhibits Osteoclast Formation and Activity in In Vitro Models for Periodontitis

2022 ◽  
Vol 9 ◽  
Author(s):  
Lucy Y. Tao ◽  
Katarzyna B. Łagosz-Ćwik ◽  
Jolanda M.A. Hogervorst ◽  
Ton Schoenmaker ◽  
Aleksander M. Grabiec ◽  
...  
Keyword(s):  
Bone Formation ◽  
Periodontal Ligament ◽  
Alveolar Bone ◽  
Fusion Gene ◽  
Cell Model ◽  
Osteoclast Formation ◽  
Periodontal Ligament Fibroblasts ◽  
Alizarin Red ◽  
Diabetes Medication ◽  
Osteoclast Precursors

Diabetes and periodontitis are comorbidities and may share common pathways. Several reports indicate that diabetes medication metformin may be beneficial for the periodontal status of periodontitis patients. Further research using appropriate cell systems of the periodontium, the tissue that surrounds teeth may reveal the possible mechanism. Periodontal ligament fibroblasts anchor teeth in bone and play a role in the onset of both alveolar bone formation and degradation, the latter by inducing osteoclast formation from adherent precursor cells. Therefore, a cell model including this type of cells is ideal to study the influence of metformin on both processes. We hypothesize that metformin will enhance bone formation, as described for osteoblasts, whereas the effects of metformin on osteoclast formation is yet undetermined. Periodontal ligament fibroblasts were cultured in the presence of osteogenic medium and 0.2 or 1 mM metformin. The influence of metformin on osteoclast formation was first studied in PDLF cultures supplemented with peripheral blood leukocytes, containing osteoclast precursors. Finally, the effect of metformin on osteoclast precursors was studied in cultures of CD14+ monocytes that were stimulated with M-CSF and receptor activator of Nf-κB ligand (RANKL). No effects of metformin were observed on osteogenesis: not on alkaline phosphatase activity, Alizarin red deposition, nor on the expression of osteogenic markers RUNX-2, Collagen I and Osteonectin. Metformin inhibited osteoclast formation and accordingly downregulated the genes involved in osteoclastogenesis: RANKL, macrophage colony stimulating factor (M-CSF) and osteoclast fusion gene DC-STAMP. Osteoclast formation on both plastic and bone as well as bone resorption was inhibited by metformin in M-CSF and RANKL stimulated monocyte cultures, probably by reduction of RANK expression. The present study unraveling the positive effect of metformin in periodontitis patients at the cellular level, indicates that metformin inhibits osteoclast formation and activity, both when orchestrated by periodontal ligament fibroblasts and in cytokine driven osteoclast formation assays. The results indicate that metformin could have a systemic beneficiary effect on bone by inhibiting osteoclast formation and activity.

Periodontal ligament fibroblasts as a cell model to study osteogenesis and osteoclastogenesis in fibrodysplasia ossificans progressiva

Bone ◽  
2018 ◽  
Vol 109 ◽  
pp. 168-177 ◽  
Author(s):  
Teun J. de Vries ◽  
Ton Schoenmaker ◽  
Dimitra Micha ◽  
Jolanda Hogervorst ◽  
Siham Bouskla ◽  
...  
Keyword(s):  
Periodontal Ligament ◽  
Cell Model ◽  
Fibrodysplasia Ossificans Progressiva ◽  
Periodontal Ligament Fibroblasts ◽  
A Cell

An osteonectinlike protein in porcine periodontal ligament and its synthesis by periodontal ligament fibroblasts

1984 ◽  
Vol 62 (6) ◽  
pp. 470-478 ◽  
Author(s):  
Safia Wasi ◽  
Kichibee Otsuka ◽  
Kam-Ling Yao ◽  
Pierre S. Tung ◽  
Jane E. Aubin ◽  
...  
Keyword(s):  
Periodontal Ligament ◽  
Culture Medium ◽  
Alveolar Bone ◽  
Polyacrylamide Gel Electrophoresis ◽  
Sodium Dodecyl ◽  
Relative Mass ◽  
Bovine Bone ◽  
Binding Studies ◽  
Periodontal Ligament Fibroblasts ◽  
Sds Page

Periodontal ligament, a soft connective tissue that lies between cementum and alveolar bone in the periodontium, has been shown to contain an osteonectinlike protein. The similarity between porcine ligament osteonectin and bovine bone osteonectin was evident from immunochemical studies, from migration characteristics on sodium dodecyl sulfate – polyacrylamide gel electrophoresis (SDS–PAGE) and from binding studies on hydroxyapatite. Using immunotransfer and immunodot analyses, ligament osteonectin was found to be extractable from tissues with 4 M guanidine–HCl (GuHCl) and 4 M GuHCl − 0.5 M EDTA and to comigrate with authentic bovine osteonectin on SDS–PAGE with a relative mass ~ 38 000. Furthermore, osteonectin from guanidine extracts of ligament was bound to hydroxyapatite in the presence of 4 M GuHCl. Immunofluorescence studies showed the osteonectin to be distributed throughout the extracellular matrix of the ligament and to be present within the ligament fibroblasts in a perinuclear, punctate distribution. Biosynthesis of osteonectin by ligament fibroblasts was studied following pulse-chase labelling with [35S]methionine and immunoprecipitation. The labelled osteonectin in the chased culture medium represented ~0.5% of the total labelled proteins secreted. It comigrated on SDS–PAGE with the corresponding labelled protein from pulsed cells and with the protein extracted from the tissue.

Gingival fibroblasts are better at inhibiting osteoclast formation than periodontal ligament fibroblasts

2006 ◽  
Vol 98 (2) ◽  
pp. 370-382 ◽  
Author(s):  
Teun J. de Vries ◽  
Ton Schoenmaker ◽  
Nutthamon Wattanaroonwong ◽  
Marije van den Hoonaard ◽  
Arlies Nieuwenhuijse ◽  
...  
Keyword(s):  
Periodontal Ligament ◽  
Osteoclast Formation ◽  
Gingival Fibroblasts ◽  
Periodontal Ligament Fibroblasts

Formation of Acellular Root Cementum in to Dental and Non-dental Hard Tissues in the Rat

1990 ◽  
Vol 69 (10) ◽  
pp. 1669-1673 ◽  
Author(s):  
W. Beertsen ◽  
V. Everts
Keyword(s):  
Periodontal Ligament ◽  
Alveolar Bone ◽  
Periodontal Ligament Fibroblasts ◽  
Dental Tissues ◽  
Dental Hard Tissues ◽  
Hard Tissues ◽  
Hard Dental Tissues

After the periodontium of the rat was wounded, the formation of acellular extrinsic fiber cementum (AEFC) did not appear to be restricted to the hard dental tissues (pre-existing cementum, dentin, and enamel). Layers resembling AEFC were also deposited along the inner wall of the alveolar bone. At the time of observation (six weeks after being wounded), cells other than fibroblast-like cells could not be distinguished close to the newly formed AEFC-like layers. We suggest that the deposition of this material was related to the activity of periodontal ligament fibroblasts.

Role of PTH1R Signaling in Prx1+ Mesenchymal Progenitors during Eruption

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.

scholarly journals Short- and long-term treatment with TNF-α inhibits the induction of osteoblastic differentiation in cyclic tensile-stretched periodontal ligament fibroblasts

2020 ◽  
Vol 42 (4) ◽  
pp. 396-406
Author(s):  
Adamantia Papadopoulou ◽  
Aurelie Cantele ◽  
Despina Koletsi ◽  
Theodore Eliades ◽  
Dimitris Kletsas
Keyword(s):  
Periodontal Ligament ◽  
Osteoblastic Differentiation ◽  
Marker Genes ◽  
Periodontal Ligament Fibroblasts ◽  
Alizarin Red ◽  
Differentiation Potential ◽  
Tnf Α ◽  
Long Term Treatment ◽  
Short And Long Term

Summary Background Cyclic tensile stretching (CTS) induces osteoblastic differentiation of periodontal ligament fibroblasts (PDLF). On the other hand, increased concentrations of tumour necrosis factor-α (TNF-α) are found in inflammatory conditions, leading to periodontal disease and tooth loss. Accordingly, our aim was to investigate the short- and long-term effect of TNF-α on the response of human PDLF to CTS and its implication on osteoblastic differentiation. Methods PDLF were either pre-incubated for 4 hours or were repeatedly exposed to TNF-α for up to 50 days and then subjected to CTS. Gene expression was determined by quantitative real-time polymerase chain reaction. Activation of mitogen-activated protein kinase (MAPK) was monitored by western analysis and cell proliferation by bromodeoxyuridine incorporation. Intracellular reactive oxygen species were determined by the 2´, 7´-dichlorofluorescein-diacetate assay and osteoblastic differentiation by Alizarin Red-S staining after an osteo-inductive period of 21 days. Results CTS of PDLF induced an immediate upregulation of the c-fos transcription factor and, further downstream the overexpression of alkaline phosphatase and osteopontin, two major osteoblast marker genes. A 4-hour pre-incubation with TNF-α repressed these effects. Similarly, long-term propagation of PDLF along with TNF-α diminished their osteoblastic differentiation capacity and suppressed cells’ CTS-elicited responses. The observed phenomena were not linked with TNF-α-induced premature senescence or oxidative stress. While CTS induced the activation of MAPKs, involved in mechanotransduction, TNF-α treatment provoked a small delay in the phosphorylation of extracellular signal-regulated kinase and c-Jun N-terminal kinase. Conclusion Increased concentrations of TNF-α, such as those recorded in many inflammatory diseases, suppress PDLF’s immediate responses to mechanical forces compromising their osteoblastic differentiation potential, possibly leading to tissue’s impaired homeostasis.

scholarly journals Diabetes Enhances Periodontal Bone Loss through Enhanced Resorption and Diminished Bone Formation

2006 ◽  
Vol 85 (6) ◽  
pp. 510-514 ◽  
Author(s):  
R. Liu ◽  
H.S. Bal ◽  
T. Desta ◽  
N. Krothapalli ◽  
M. Alyassi ◽  
...  
Keyword(s):  
Bone Loss ◽  
Bone Formation ◽  
Alveolar Bone ◽  
Diabetic Rats ◽  
New Bone Formation ◽  
Periodontal Ligament Fibroblasts ◽  
Zdf Rat ◽  
Pdl Cells ◽  
Periodontal Bone Loss

Using a ligature-induced model in type-2 Zucker diabetic fatty (ZDF) rat and normoglycemic littermates, we investigated whether diabetes primarily affects periodontitis by enhancing bone loss or by limiting osseous repair. Diabetes increased the intensity and duration of the inflammatory infiltrate (P < 0.05). The formation of osteoclasts and percent eroded bone after 7 days of ligature placement was similar, while four days after removal of ligatures, the type 2 diabetic group had significantly higher osteoclast numbers and activity (P < 0.05). The amount of new bone formation following resorption was 2.4- to 2.9-fold higher in normoglycemic vs. diabetic rats (P < 0.05). Diabetes also increased apoptosis and decreased the number of bone-lining cells, osteoblasts, and periodontal ligament fibroblasts (P < 0.05). Thus, diabetes caused a more persistent inflammatory response, greater loss of attachment and more alveolar bone resorption, and impaired new bone formation. The latter may be affected by increased apoptosis of bone-lining and PDL cells.

scholarly journals Distinguish fatty acids impact survival, differentiation and cellular function of periodontal ligament fibroblasts

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Judit Symmank ◽  
Martin Chorus ◽  
Sophie Appel ◽  
Jana Marciniak ◽  
Isabel Knaup ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Periodontal Ligament ◽  
Alveolar Bone ◽  
Tooth Movement ◽  
Orthodontic Tooth Movement ◽  
Serum Levels ◽  
Osteoblastic Differentiation ◽  
Mechanical Stimuli ◽  
Periodontal Ligament Fibroblasts

Abstract Alveolar bone (AB) remodeling is necessary for the adaption to mechanical stimuli occurring during mastication and orthodontic tooth movement (OTM). Thereby, bone degradation and assembly are strongly regulated processes that can be altered in obese patients. Further, increased fatty acids (FA) serum levels affect bone remodeling cells and we, therefore, investigated whether they also influence the function of periodontal ligament fibroblast (PdLF). PdLF are a major cell type regulating the differentiation and function of osteoblasts and osteoclasts localized in the AB. We stimulated human PdLF (HPdLF) in vitro with palmitic (PA) or oleic acid (OA) and analyzed their metabolic activity, growth, survival and expression of osteogenic markers and calcium deposits. Our results emphasize that PA increased cell death of HPdLF, whereas OA induced their osteoblastic differentiation. Moreover, quantitative expression analysis of OPG and RANKL revealed altered levels in mechanically stimulated PA-treated HPdLF. Furthermore, osteoclasts stimulated with culture medium of mechanical stressed FA-treated HPdLF revealed significant changes in cell differentiation upon FA-treatment. For the first time, our results highlight a potential role of specific FA in the function of HPdLF-modulated AB remodeling and help to elucidate the complex interplay of bone metabolism, mechanical stimulation and obesity-induced alterations.

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