scholarly journals The effect of Activin‐A on periodontal ligament fibroblasts‐mediated osteoclast formation in healthy donors and in patients with fibrodysplasia ossificans progressiva

2018 ◽  
Vol 234 (7) ◽  
pp. 10238-10247 ◽  
Author(s):  
Ton Schoenmaker ◽  
Fenne Wouters ◽  
Dimitra Micha ◽  
Tim Forouzanfar ◽  
Coen Netelenbos ◽  
...  
Keyword(s):  
Periodontal Ligament ◽  
Activin A ◽  
Osteoclast Formation ◽  
Fibrodysplasia Ossificans Progressiva ◽  
Periodontal Ligament Fibroblasts ◽  
Healthy Donors

scholarly journals Activin-A Induces Early Differential Gene Expression Exclusively in Periodontal Ligament Fibroblasts from Fibrodysplasia Ossificans Progressiva Patients

Biomedicines ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 629
Author(s):  
Ton Schoenmaker ◽  
Michal Mokry ◽  
Dimitra Micha ◽  
Coen Netelenbos ◽  
Nathalie Bravenboer ◽  
...  
Keyword(s):  
Gene Expression ◽  
Heterotopic Ossification ◽  
Rna Sequencing ◽  
Differential Gene Expression ◽  
Periodontal Ligament ◽  
Activin A ◽  
Fibrodysplasia Ossificans Progressiva ◽  
Sequencing Analysis ◽  
Periodontal Ligament Fibroblasts ◽  
Differential Gene

Fibrodysplasia Ossificans Progressiva (FOP) is a rare genetic disease characterized by heterotopic ossification (HO). It is caused by mutations in the Activin receptor type 1 (ACVR1) gene, resulting in enhanced responsiveness to ligands, specifically to Activin-A. Though it has been shown that capturing Activin-A protects against heterotopic ossification in animal models, the exact underlying mechanisms at the gene expression level causing ACVR1 R206H-mediated ossifications and progression are thus far unknown. We investigated the early transcriptomic changes induced by Activin-A of healthy control and patient-derived periodontal ligament fibroblasts (PLF) isolated from extracted teeth by RNA sequencing analysis. To study early differences in response to Activin-A, periodontal ligament fibroblasts from six control teeth and from six FOP patient teeth were cultured for 24 h without and with 50 ng/mL Activin-A and analyzed with RNA sequencing. Pathway analysis on genes upregulated by Activin-A in FOP cells showed an association with pathways involved in, among others, Activin, TGFβ, and BMP signaling. Differential gene expression induced by Activin-A was exclusively seen in the FOP cells. Median centered supervised gene expression analysis showed distinct clusters of up- and downregulated genes in the FOP cultures after stimulation with Activin-A. The upregulated genes with high fold changes like SHOC2, TTC1, PAPSS2, DOCK7, and LOX are all associated with bone metabolism. Our open-ended approach to investigating the early effect of Activin-A on gene expression in control and FOP PLF shows that the molecule exclusively induces differential gene expression in FOP cells and not in control cells.

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

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

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.

scholarly journals Oestrogen inhibits osteoclast formation induced by periodontal ligament fibroblasts

2011 ◽  
Vol 56 (3) ◽  
pp. 212-219 ◽  
Author(s):  
Nutthamon Wattanaroonwong ◽  
Ton Schoenmaker ◽  
Teun J. de Vries ◽  
Vincent Everts
Keyword(s):  
Periodontal Ligament ◽  
Osteoclast Formation ◽  
Periodontal Ligament Fibroblasts

Fibrodysplasia Ossificans Progressiva – FOP

2018 ◽  
Vol 27 (04) ◽  
pp. 215-221
Author(s):  
R. Morhart ◽  
O. Semler ◽  
L. Seefried
Keyword(s):  
Hallux Valgus ◽  
Activin A ◽  
Fibrodysplasia Ossificans Progressiva ◽  
Intramuskuläre Injektionen ◽  
Sind Eine

ZusammenfassungBei der Fibrodysplasia ossificans progressiva (FOP) besteht aufgrund einer aktivierenden Mutation im Gen für den Activin A Rezeptor Typ 1 (ACVR1 / ALK2), eine Prädisposition zu heterotoper Knochenbildung in Weichgeweben, insbesondere der Muskulatur. Die Prävalenz der Erkrankung wird in einer Größenordnung von 1 pro 1–2 Mio. angegeben. Klinisch kommt es intrauterin zu Fehlbildungen, z. B. zu einem bds. Hallux valgus, der bei der überwiegenden Mehrheit der Patienten bereits bei Geburt besteht. Postnatal kommt es meist in den ersten Lebensjahren beginnend im Schulter-/ Nackenbereich episodenartig bereits nach kleineren Verletzungen zu schmerzhaften Weichteilreaktionen, sogenannten flareups die nachfolgend im Sinne einer enchondralen Ossifikation verknöchern. Die Akkumulation dieser irreversiblen Verknöcherungen im Weichgewebe bedingt eine zunehmende Einschränkung der Beweglichkeit bis hin zur kompletten Einsteifung des Körpers. Letztlich kommt es durch die fortschreitende Rigidität des Thorax zu einer respiratorischen Insuffizienz und kardialer Dekompensation.Therapeutisch steht im Vordergrund die Vermeidung von Traumata als Auslöser für die Entstehung extraossären Knochengewebes, insbesondere auch der Verzicht auf unnötige iatrogene Schädigungen durch Operationen, Biopsien und intramuskuläre Injektionen. Supportiv sind eine adäquate Hilfsmittelversorgung, psychologische Unterstützung und eine analgetische Versorgung erforderlich. Im Falle eines Traumas werden kurzfristig hochdosiert Glucocorticoide empfohlen, um das Risiko und Ausmaß der flare-ups und nachfolgender Verknöcherungen zu reduzieren. Ergänzend können NSAR hilfreich sein. Derzeit werden unterschiedliche neue Therapieansätze entwickelt. Am weitesten fortgeschritten ist dabei der Retinolsäure Rezeptor Gamma (RARg) Agonist Palovarotene, der durch Interferenz mit der ALK2 vermittelten Signalkaskade einen zentralen Punkt im Pathomechanismus der Erkrankung adressiert.

An Acvr1[R258G] ‘conditional on' mouse model of atypical fibrodysplasia ossificans progressiva (FOP) is Activin A dependent

2019 ◽  
Author(s):  
Lily Huang ◽  
Chris Schoenherr ◽  
Lili Wang ◽  
Xialing Wen ◽  
Joyce McClain ◽  
...  
Keyword(s):  
Mouse Model ◽  
Activin A ◽  
Fibrodysplasia Ossificans Progressiva
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