Mechanisms of palmitate-induced lipotoxicity in osteocytes

Background: Lipotoxicity is defined as cellular toxicity observed in the presence of an abnormal accumulation of fat and adipocyte-derived factors in non-fat tissues. Palmitic acid (PA), an abundant fatty acid in the bone marrow and particularly in osteoporotic bones, affects osteoblastogenesis and...

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Autores:: Al Saedi, Ahmed
Bermeo, Sandra
Plotkin, Lilian
Myers, Damian E.
Duque, Gustavo

Tipo de recurso:

Fecha de publicación:: 2019

Institución:: Universidad Simón Bolívar

Repositorio:: Repositorio Digital USB

Idioma:: eng

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dc.title.eng.fl_str_mv	Mechanisms of palmitate-induced lipotoxicity in osteocytes
title	Mechanisms of palmitate-induced lipotoxicity in osteocytes
spellingShingle	Mechanisms of palmitate-induced lipotoxicity in osteocytes Palmitic acid Osteocytes Lipotoxicity Fatty acids Osteoporosis Apoptosis Autophagy
title_short	Mechanisms of palmitate-induced lipotoxicity in osteocytes
title_full	Mechanisms of palmitate-induced lipotoxicity in osteocytes
title_fullStr	Mechanisms of palmitate-induced lipotoxicity in osteocytes
title_full_unstemmed	Mechanisms of palmitate-induced lipotoxicity in osteocytes
title_sort	Mechanisms of palmitate-induced lipotoxicity in osteocytes
dc.creator.fl_str_mv	Al Saedi, Ahmed Bermeo, Sandra Plotkin, Lilian Myers, Damian E. Duque, Gustavo
dc.contributor.author.none.fl_str_mv	Al Saedi, Ahmed Bermeo, Sandra Plotkin, Lilian Myers, Damian E. Duque, Gustavo
dc.subject.eng.fl_str_mv	Palmitic acid Osteocytes Lipotoxicity Fatty acids Osteoporosis Apoptosis Autophagy
topic	Palmitic acid Osteocytes Lipotoxicity Fatty acids Osteoporosis Apoptosis Autophagy
description	Background: Lipotoxicity is defined as cellular toxicity observed in the presence of an abnormal accumulation of fat and adipocyte-derived factors in non-fat tissues. Palmitic acid (PA), an abundant fatty acid in the bone marrow and particularly in osteoporotic bones, affects osteoblastogenesis and osteoblast function, decreasing their survival through induction of apoptosis and dysfunctional autophagy. In this study, we hypothesized that PA also has a lipotoxic effect on osteocytes in vitro. Methods: Initially, we tested the effect of PA on osteocyte-derived factors DKK1, sclerostin and RANKL. Then, we tested whether PA affects survival and causes apoptosis in osteocytes. Subsequently, we investigated the effect of PA on autophagy by detecting the membrane component LC3-II (Western blot) and staining them and lysosomes with Lysotracker Red dye. Results: PA decreases RANKL, DKK1 and sclerostin expression in osteocytes. In addition, we found that PA induces apoptosis and reduces osteocyte survival. PA also caused autophagy failure identified by a significant increase in LC3-II and a reduced number of autophagosomes/lysosomes in the cytoplasm. Conclusion: In addition to the effects of PA on RANKL, DKK1 and sclerostin expression, which could have significant deleterious impact on bone cell coupling and bone turnover, PA also induced apoptosis and reduced autophagy in osteocytes. Considering that apoptosis and cell dysfunction are two common changes occurring in the osteocytes of osteoporotic bone, our findings suggest that PA could play a role in the pathogenesis of the disease. Suppression of these effects could bring new potential targets for therapeutic interventions in the future.
publishDate	2019
dc.date.accessioned.none.fl_str_mv	2019-07-22T19:42:50Z
dc.date.available.none.fl_str_mv	2019-07-22T19:42:50Z
dc.date.issued.none.fl_str_mv	2019-06
dc.type.eng.fl_str_mv	article
dc.type.coar.fl_str_mv	http://purl.org/coar/resource_type/c_6501
dc.identifier.issn.none.fl_str_mv	87563282
dc.identifier.uri.none.fl_str_mv	https://hdl.handle.net/20.500.12442/3607
identifier_str_mv	87563282
url	https://hdl.handle.net/20.500.12442/3607
dc.language.iso.eng.fl_str_mv	eng
language	eng
dc.rights.*.fl_str_mv	Attribution-NonCommercial-NoDerivatives 4.0 Internacional
dc.rights.coar.fl_str_mv	http://purl.org/coar/access_right/c_abf2
dc.rights.uri.*.fl_str_mv	http://creativecommons.org/licenses/by-nc-nd/4.0/
rights_invalid_str_mv	Attribution-NonCommercial-NoDerivatives 4.0 Internacional http://creativecommons.org/licenses/by-nc-nd/4.0/ http://purl.org/coar/access_right/c_abf2
dc.publisher.spa.fl_str_mv	Elsevier
dc.source.eng.fl_str_mv	Revista BONE
institution	Universidad Simón Bolívar
dc.source.uri.eng.fl_str_mv	https://doi.org/10.1016/j.bone.2019.06.016
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spelling	Al Saedi, Ahmed7ae05a3f-ed6d-409f-987e-6184f911fe1cBermeo, Sandra5adcb3ad-0b9f-41f8-8a5f-a4d6086d31efPlotkin, Lilian972d072d-a4f0-4168-bd2e-87fbd12f6398Myers, Damian E.a0b8df76-235d-4377-a9fb-4af5078eeff2Duque, Gustavof99ef41b-e311-4165-bbc4-73e084153d5f2019-07-22T19:42:50Z2019-07-22T19:42:50Z2019-0687563282https://hdl.handle.net/20.500.12442/3607Background: Lipotoxicity is defined as cellular toxicity observed in the presence of an abnormal accumulation of fat and adipocyte-derived factors in non-fat tissues. Palmitic acid (PA), an abundant fatty acid in the bone marrow and particularly in osteoporotic bones, affects osteoblastogenesis and osteoblast function, decreasing their survival through induction of apoptosis and dysfunctional autophagy. In this study, we hypothesized that PA also has a lipotoxic effect on osteocytes in vitro. Methods: Initially, we tested the effect of PA on osteocyte-derived factors DKK1, sclerostin and RANKL. Then, we tested whether PA affects survival and causes apoptosis in osteocytes. Subsequently, we investigated the effect of PA on autophagy by detecting the membrane component LC3-II (Western blot) and staining them and lysosomes with Lysotracker Red dye. Results: PA decreases RANKL, DKK1 and sclerostin expression in osteocytes. In addition, we found that PA induces apoptosis and reduces osteocyte survival. PA also caused autophagy failure identified by a significant increase in LC3-II and a reduced number of autophagosomes/lysosomes in the cytoplasm. Conclusion: In addition to the effects of PA on RANKL, DKK1 and sclerostin expression, which could have significant deleterious impact on bone cell coupling and bone turnover, PA also induced apoptosis and reduced autophagy in osteocytes. Considering that apoptosis and cell dysfunction are two common changes occurring in the osteocytes of osteoporotic bone, our findings suggest that PA could play a role in the pathogenesis of the disease. Suppression of these effects could bring new potential targets for therapeutic interventions in the future.engElsevierAttribution-NonCommercial-NoDerivatives 4.0 Internacionalhttp://creativecommons.org/licenses/by-nc-nd/4.0/http://purl.org/coar/access_right/c_abf2Revista BONEhttps://doi.org/10.1016/j.bone.2019.06.016Palmitic acidOsteocytesLipotoxicityFatty acidsOsteoporosisApoptosisAutophagyMechanisms of palmitate-induced lipotoxicity in osteocytesarticlehttp://purl.org/coar/resource_type/c_6501E.A. Zimmermann, E. Schaible, H. Bale, H.D. Barth, S.Y. Tang, P. Reichert, B. Busse, T. Alliston, J.W. Ager 3rd, R.O. Ritchie, Age-related changes in the plasticity and toughness of human cortical bone at multiple length scales, Proc. Natl. Acad. Sci. U. S. A. 108 (35) (2011) 14416–14421.D.P. 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Mechanisms of palmitate-induced lipotoxicity in osteocytes

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