Adrenomedullin and truncated peptide adrenomedullin(22-52) affect chondrocyte response to apoptotis in vitro: downregulation of FAS protects chondrocyte from cell death.
Adrenomedullin
/ metabolism
Animals
Apoptosis
/ drug effects
Calcitonin Receptor-Like Protein
/ metabolism
Cartilage, Articular
/ metabolism
Cattle
Chondrocytes
/ drug effects
Down-Regulation
/ drug effects
Fas Ligand Protein
/ pharmacology
Hypoxia-Inducible Factor 1, alpha Subunit
/ metabolism
Peptide Fragments
/ pharmacology
Receptor Activity-Modifying Protein 2
/ metabolism
Signal Transduction
/ drug effects
fas Receptor
/ metabolism
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
07 10 2020
07 10 2020
Historique:
received:
01
04
2020
accepted:
31
08
2020
entrez:
8
10
2020
pubmed:
9
10
2020
medline:
15
12
2020
Statut:
epublish
Résumé
Chondrocyte apoptosis may have a pivotal role in the development of osteoarthritis. Interest has increased in the use of anti-apoptotic compounds to protect against osteoarthritis development. In this work, we investigated the effect of adrenomedullin (AM), a 52 amino-acid hormone peptide, and a 31 amino-acid truncated form, AM(22-52), on chondrocyte apoptosis. Bovine articular chondrocytes (BACs) were cultured under hypoxic conditions to mimic cartilage environment and then treated with Fas ligand (Fas-L) to induce apoptosis. The expression of AM and its calcitonin receptor-like receptor (CLR)/receptor activity-modifying protein (RAMP) (receptor/co-receptor) was assessed by immunostaining. We evaluated the effect of AM and AM(22-52) on Fas-L-induced chondrocyte apoptosis. FAS expression was appreciated by RT-qPCR and immunostainings. The expression of hypoxia-inducible factor 1α (HIF-1α), CLR and one co-receptor (RAMP2) was evidenced. With BACs under hypoxia, cyclic adenosine monophosphate production increased dose-dependently with AM stimulation. AM significantly decreased caspase-3 activity (mean 35% decrease; p = 0.03) as a marker of Fas-L-induced apoptosis. Articular chondrocytes treated with AM showed significantly reduced cell death, along with downregulated Fas expression and production, as compared with AM(22-52). AM decreased articular chondrocyte apoptosis by downregulating a Fas receptor. These findings may pave the way for novel therapeutic approaches in osteoarthritis.
Identifiants
pubmed: 33028903
doi: 10.1038/s41598-020-73924-1
pii: 10.1038/s41598-020-73924-1
pmc: PMC7541509
doi:
Substances chimiques
Calcitonin Receptor-Like Protein
0
Fas Ligand Protein
0
Hypoxia-Inducible Factor 1, alpha Subunit
0
Peptide Fragments
0
Receptor Activity-Modifying Protein 2
0
adrenomedullin (22-52)
0
fas Receptor
0
Adrenomedullin
148498-78-6
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
16740Références
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