Adrenomedullin and truncated peptide adrenomedullin(22-52) affect chondrocyte response to apoptotis in vitro: downregulation of FAS protects chondrocyte from cell death
| Autor: | Hang-Korng Ea, Frédéric Lioté, Hilène Lin, Narjes Hafsia, Marie-Dominique Ah-Kioon, Frédéric Velard, Aurore Chatron-Colliet, Dominique Come, Martine Cohen-Solal |
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| Přispěvatelé: | Biologie de l'Os et du Cartilage : Régulations et Ciblages Thérapeutiques (BIOSCAR (UMR_S_1132 / U1132)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Centre Viggo-Petersen, Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université de Paris - UFR Médecine Paris Centre [Santé] (UP Médecine Paris Centre), Université de Paris (UP) |
| Rok vydání: | 2020 |
| Předmět: |
Cartilage
Articular 0301 basic medicine Cell biology Programmed cell death Fas Ligand Protein [SDV]Life Sciences [q-bio] lcsh:Medicine Down-Regulation Apoptosis Receptor Activity-Modifying Protein 2 Article Fas ligand Chondrocyte Adrenomedullin 03 medical and health sciences Rheumatic diseases Chondrocytes 0302 clinical medicine Rheumatology medicine Animals fas Receptor lcsh:Science Receptor 030203 arthritis & rheumatology Multidisciplinary Chemistry lcsh:R Calcitonin Receptor-Like Protein Hypoxia-Inducible Factor 1 alpha Subunit Fas receptor Peptide Fragments 030104 developmental biology medicine.anatomical_structure RAMP2 Cancer research lcsh:Q Cattle Signal Transduction |
| Zdroj: | Scientific Reports Scientific Reports, Nature Publishing Group, 2020, 10, ⟨10.1038/s41598-020-73924-1⟩ Scientific Reports, Vol 10, Iss 1, Pp 1-12 (2020) |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/s41598-020-73924-1 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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