Trehalose reduces bone loss in experimental biliary cirrhosis rats via ERK phosphorylation regulation by enhancing autophagosome formation.
3T3 Cells
Animals
Autophagosomes
/ metabolism
Bone Diseases, Metabolic
/ metabolism
Bone Resorption
/ metabolism
Cell Differentiation
/ physiology
Disease Models, Animal
Liver Cirrhosis, Biliary
/ metabolism
MAP Kinase Signaling System
/ physiology
Male
Mice
Osteoblasts
/ metabolism
Osteoclasts
/ metabolism
Osteogenesis
/ physiology
Osteoporosis
/ metabolism
Phosphorylation
/ physiology
RANK Ligand
/ metabolism
Rats
Rats, Sprague-Dawley
Signal Transduction
/ physiology
Trehalose
/ metabolism
ERK phosphorylation
autophagosomes
osteoclastogenesis
osteoporosis in PBC
trehalose
Journal
FASEB journal : official publication of the Federation of American Societies for Experimental Biology
ISSN: 1530-6860
Titre abrégé: FASEB J
Pays: United States
ID NLM: 8804484
Informations de publication
Date de publication:
06 2020
06 2020
Historique:
received:
10
10
2019
revised:
07
04
2020
accepted:
13
04
2020
pubmed:
6
5
2020
medline:
16
1
2021
entrez:
6
5
2020
Statut:
ppublish
Résumé
Bone loss is a severe complication of primary biliary cirrhosis (PBC). Trehalose was intermittently administered in bile duct-ligated (BDL) male rats, a PBC-related osteoporosis model, for 4 weeks to reduce osteoporosis. Femoral bones were assessed ex vivo by micro computed tomography (CT) and histomorphometry. The potential mechanisms related to the reduction of osteoporosis were explored by evaluating the effect of trehalose on osteoblast autophagy, osteogenesis, osteoclastogenesis, and ERK phosphorylation. The results demonstrated that trehalose reduced osteoporosis of BDL rats and decreased osteoblast-mediated osteoclast differentiation by enhancing osteoblast autophagy to regulate osteoprotegerin (OPG) secretion. Hydroxychloroquine (HCQ) increased the expression of OPG and OPG/receptor activator genes for nuclear factor-κB ligand (RANKL) ratio, and reduced osteoblast-mediated osteoclastogenesis by inhibiting autophagy flux and inducing autophagosome formation. Furthermore, trehalose increased the phosphorylation of ERK1/2 in MC3T3-E1 cells, and the ERK inhibitor PD98059 reversed the upregulation of OPG gene and reduction of trehalose-induced osteoclastogeneis. The treatment with HCQ markedly increased the ERK phosphorylation. The correlation between autophagosome formation and ERK phosphorylation was confirmed in autophagy proteins (ATG) 4B or ATG5-deficient cells. Thus, trehalose could decrease osteoblast-mediated osteoclastogenesis and reduce PBC-related bone loss by regulating ERK phosphorylation via autophagosome formation.
Identifiants
pubmed: 32367591
doi: 10.1096/fj.201902528RRR
doi:
Substances chimiques
RANK Ligand
0
Trehalose
B8WCK70T7I
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
8402-8415Informations de copyright
© 2020 The Authors. The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.
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