GW9508, a free fatty acid receptor agonist, specifically induces cell death in bone resorbing precursor cells through increased oxidative stress from mitochondrial origin - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Experimental Cell Research Année : 2013

GW9508, a free fatty acid receptor agonist, specifically induces cell death in bone resorbing precursor cells through increased oxidative stress from mitochondrial origin

Résumé

GW9508 is a free fatty acid receptor agonist able to protect from ovariectomy-induced bone loss in vivo thought inhibition of osteoclast differentiation in a G-coupled Protein Receptor 40 (GPR40)-dependent way. In this study, we questioned whether higher doses of GW9508 may also influence resorbing cell viability specifically. Interestingly, GW9508 at 100M altered osteoclast precursor (OcP) viability while it had positive effects on osteoblastic precursors suggesting an activity dependent on the cell lineage. According to 7-AAD/Annexin-V staining, induced OcP cell death was found to be associated with necrosis mechanisms. Consistently, GW9508 led to a sustained establishment of oxidative stress from mitochondrial origin. In contrast to previous observations on osteoclast differentiation inhibition, OcP viability targeted by high doses of GW9508 appeared to be independent of GPR40 involvement. Although mediating structures remain to be determined, our data demonstrate for the first time that this fatty acid receptor agonist driving OcP specific cell death may now open new perspectives regarding therapeutic strategies in osteolytic disorders.

Dates et versions

hal-00961341 , version 1 (19-03-2014)

Identifiants

Citer

Claire C. Philippe, Fabien F. Wauquier, Laurent L. Leotoing, Véronique Coxam, Y. Wittrant. GW9508, a free fatty acid receptor agonist, specifically induces cell death in bone resorbing precursor cells through increased oxidative stress from mitochondrial origin. Experimental Cell Research, 2013, 319 (19), pp.3035-3041. ⟨10.1016/j.yexcr.2013.08.013⟩. ⟨hal-00961341⟩
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