The effect of Activin-A on periodontal ligament fibroblasts-mediated osteoclast formation in healthy donors and in patients with fibrodysplasia ossificans progressiva.
Activin Receptors, Type I
/ metabolism
Activins
/ pharmacology
Adolescent
Adult
Case-Control Studies
Cell Communication
/ drug effects
Cell Differentiation
/ drug effects
Cell Proliferation
/ drug effects
Cells, Cultured
Coculture Techniques
Female
Fibroblasts
/ drug effects
Humans
Inhibitor of Differentiation Protein 1
/ metabolism
Lipopolysaccharide Receptors
/ metabolism
Male
Myositis Ossificans
/ metabolism
Osteoclasts
/ drug effects
Osteogenesis
/ drug effects
Periodontal Ligament
/ drug effects
Phosphorylation
Signal Transduction
Smad3 Protein
/ metabolism
Tacrolimus Binding Protein 1A
/ metabolism
Young Adult
Activin-A
fibrodysplasia ossificans progressiva (FOP)
osteoclastogenesis
osteogenesis
periodontal ligament fibroblasts (PLF)
Journal
Journal of cellular physiology
ISSN: 1097-4652
Titre abrégé: J Cell Physiol
Pays: United States
ID NLM: 0050222
Informations de publication
Date de publication:
07 2019
07 2019
Historique:
received:
25
05
2018
accepted:
09
10
2018
pubmed:
13
11
2018
medline:
6
5
2020
entrez:
13
11
2018
Statut:
ppublish
Résumé
Fibrodysplasia ossificans progressiva (FOP) is a genetic disease characterized by heterotopic ossification (HO). The disease is caused by a mutation in the activin receptor type 1 (ACVR1) gene that enhances this receptor's responsiveness to Activin-A. Binding of Activin-A to the mutated ACVR1 receptor induces osteogenic differentiation. Whether Activin-A also affects osteoclast formation in FOP is not known. Therefore we investigated its effect on the osteoclastogenesis-inducing potential of periodontal ligament fibroblasts (PLF) from teeth of healthy controls and patients with FOP. We used western blot analysis of phosphorylated SMAD3 (pSMAD3) and quantitative polymerase chain reaction to assess the effect of Activin-A on the PLF. PLF-induced osteoclast formation and gene expression were studied by coculturing control and FOP PLF with CD14-positive osteoclast precursor cells from healthy donors. Osteoclast formation was also assessed in control CD14 cultures stimulated by macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor kappa-B ligand (RANK-L). Although Activin-A increased activation of the pSMAD3 pathway in both control and FOP PLF, it increased ACVR1, FK binding protein 12 (FKBP12), an inhibitor of DNA binding 1 protein (ID-1) expression only in FOP PLF. Activin-A inhibited PLF mediated osteoclast formation albeit only significantly when induced by FOP PLF. In these cocultures, it reduced M-CSF and dendritic cell-specific transmembrane protein (DC-STAMP) expression. Activin-A also inhibited osteoclast formation in M-CSF and RANK-L mediated monocultures of CD14+ cells by inhibiting their proliferation. This study brings new insight on the role of Activin A in osteoclast formation, which may further add to understanding FOP pathophysiology; in addition to the known Activin-A-mediated HO, this study shows that Activin-A may also inhibit osteoclast formation, thereby further promoting HO formation.
Identifiants
pubmed: 30417373
doi: 10.1002/jcp.27693
pmc: PMC6587553
doi:
Substances chimiques
CD14 protein, human
0
ID1 protein, human
0
Inhibitor of Differentiation Protein 1
0
Lipopolysaccharide Receptors
0
SMAD3 protein, human
0
Smad3 Protein
0
activin A
0
Activins
104625-48-1
ACVR1 protein, human
EC 2.7.11.30
Activin Receptors, Type I
EC 2.7.11.30
Tacrolimus Binding Protein 1A
EC 5.2.1.-
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
10238-10247Informations de copyright
© 2018 Authors. Journal of Cellular Physiology Published by Wiley Periodicals, Inc.
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