Activation of G
Activins
/ metabolism
Alkaline Phosphatase
/ metabolism
Animals
Bacterial Proteins
/ metabolism
Bacterial Toxins
/ metabolism
Bone Morphogenetic Protein 4
/ metabolism
Calcium Signaling
Cell Line
GTP-Binding Protein alpha Subunits, Gq-G11
/ metabolism
Mice
Models, Biological
Myoblasts
/ metabolism
Myositis Ossificans
/ pathology
Osteoblasts
/ metabolism
Signal Transduction
Smad Proteins
/ metabolism
Activin A
Alk2
BMP
FOP
Osteoblast differentiation
Smad
Journal
Bone
ISSN: 1873-2763
Titre abrégé: Bone
Pays: United States
ID NLM: 8504048
Informations de publication
Date de publication:
10 2019
10 2019
Historique:
received:
11
09
2018
revised:
29
07
2019
accepted:
30
07
2019
pubmed:
4
8
2019
medline:
17
9
2020
entrez:
4
8
2019
Statut:
ppublish
Résumé
The human disease fibrodysplasia ossificans progressiva (FOP) is a rare and highly disabling disorder of extensive heterotopic bone growth that is caused by a point mutation (R206H) in the activation domain of Alk2, a BMP (bone morphogenic protein) type 1 receptor. The mutation leads to extensive BMP-signaling induced by Activin A, which is normally an antagonist for wildtype receptors, resulting in excessive and uncontrolled bone formation. Here, we studied the effects of Pasteurella multocida toxin (PMT), which activates osteoclasts and inhibits osteoblast activity, in C2C12 myoblasts expressing the mutant Alk2(R206H) receptor as model of FOP. In our study, we mainly used alkaline phosphatase (ALP) activity as marker to determine osteoblast differentiation. BMP-4 stimulated an increase in ALP activity in C2C12-Alk2wt and C2C12-Alk2(R206H) cells. By contrast, Activin A only induced ALP activity in C2C12-Alk2(R206H) cells. In both cases, PMT acted as a potent inhibitor of ALP activity. PMT-induced inhibition of ALP activity was paralleled by a constitutive activation of the heterotrimeric G
Identifiants
pubmed: 31376533
pii: S8756-3282(19)30305-9
doi: 10.1016/j.bone.2019.07.031
pii:
doi:
Substances chimiques
Bacterial Proteins
0
Bacterial Toxins
0
Bone Morphogenetic Protein 4
0
Pasteurella multocida toxin
0
Smad Proteins
0
activin A
0
Activins
104625-48-1
Alkaline Phosphatase
EC 3.1.3.1
GTP-Binding Protein alpha Subunits, Gq-G11
EC 3.6.5.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
592-601Informations de copyright
Copyright © 2019 Elsevier Inc. All rights reserved.