Mostrar el registro sencillo del ítem

dc.contributor.authorAl Saedi, Ahmed
dc.contributor.authorBermeo, Sandra
dc.contributor.authorPlotkin, Lilian
dc.contributor.authorMyers, Damian E.
dc.contributor.authorDuque, Gustavo
dc.description.abstractBackground: 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.eng
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 Internacional*
dc.sourceRevista BONEeng
dc.subjectPalmitic acideng
dc.subjectFatty acidseng
dc.titleMechanisms of palmitate-induced lipotoxicity in osteocyteseng
dcterms.referencesE.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.eng
dcterms.referencesD.P. Fyhrie, B.A. Christiansen, Bone material properties and skeletal fragility, Calcif. Tissue Int. 97 (3) (2015) 213–228.eng
dcterms.referencesS. Muruganandan, R. Govindarajan, C.J. Sinal, Bone marrow adipose tissue and skeletal health, Current Osteoporosis Reports 16 (4) (2018) 434–442.eng
dcterms.referencesL. Singh, S. Tyagi, D. Myers, G. Duque, Good, bad, or ugly: the biological roles of bone marrow fat, Current Osteoporosis Reports 16 (2) (2018) 130–137.eng
dcterms.referencesK. Gunaratnam, C. Vidal, J.M. Gimble, G. Duque, Mechanisms of palmitate-induced lipotoxicity in human osteoblasts, Endocrinology 155 (1) (2014) 108–116.eng
dcterms.referencesK. Gunaratnam, C. Vidal, R. Boadle, C. Thekkedam, G. Duque, Mechanisms of palmitate-induced cell death in human osteoblasts, Biology open 2 (12) (2013) 1382–1389.eng
dcterms.referencesA.G. Veldhuis-Vlug, C.J. Rosen, Clinical implications of bone marrow adiposity, J. Intern. Med. 283 (2) (2018) 121–139.eng
dcterms.referencesL.F. Bonewald, The amazing osteocyte, J. Bone Miner. Res. Off. J. Am. Soc. Bone Miner. Res. 26 (2) (2011) 229–238.eng
dcterms.referencesL.F. Bonewald, Osteocytes as dynamic multifunctional cells, Ann. N. Y. Acad. Sci. 1116 (2007) 281–290.eng
dcterms.referencesR.S. Weinstein, S.C. Manolagas, Apoptosis and osteoporosis, Am. J. Med. 108 (2) (2000) 153–164.eng
dcterms.referencesS.C. Manolagas, A.M. Parfitt, What old means to bone, Trends Endocrinol Metab 21 (6) (2010) 369–374.eng
dcterms.referencesL.I. Plotkin, Apoptotic osteocytes and the control of targeted bone resorption, Current osteoporosis reports 12 (1) (2014) 121–126.eng
dcterms.referencesG. Gu, M. Mulari, Z. Peng, T.A. Hentunen, H.K. Vaananen, Death of osteocytes turns off the inhibition of osteoclasts and triggers local bone resorption, Biochem. Biophys. Res. Commun. 335 (4) (2005) 1095–1101.eng
dcterms.referencesO.D. Kennedy, M.B. Schaffler, The roles of osteocyte signaling in bone, J. Am. Acad. Orthop. Surg. 20 (10) (2012) 670–671.eng
dcterms.referencesH.M. Frost, Tetracycline-based histological analysis of bone remodeling, Calcif. Tissue Res. 3 (3) (1969) 211–237.eng
dcterms.referencesR.H. Unger, L. Orci, Lipoapoptosis: its mechanism and its diseases, Biochim. Biophys. Acta 1585 (2–3) (2002) 202–212.eng
dcterms.referencesL. Martino, M. Masini, M. Novelli, P. Beffy, M. Bugliani, L. Marselli, P. Masiello, P. Marchetti, V. De Tata, Palmitate activates autophagy in INS-1E beta-cells and in isolated rat and human pancreatic islets, PLoS One 7 (5) (2012) e36188.eng
dcterms.referencesT. Nakashima, M. Hayashi, T. Fukunaga, K. Kurata, M. Oh-Hora, J.Q. Feng, L.F. Bonewald, T. Kodama, A. Wutz, E.F. Wagner, J.M. Penninger, H. Takayanagi, Evidence for osteocyte regulation of bone homeostasis through RANKL expression, Nat. Med. 17 (10) (2011) 1231–1234.eng
dcterms.referencesA. Elbaz, X. Wu, D. Rivas, J.M. Gimble, G. Duque, Inhibition of fatty acid biosynthesis prevents adipocyte lipotoxicity on human osteoblasts in vitro, J. Cell. Mol. Med. 14 (4) (2010) 982–991.eng
dcterms.referencesH.M. Davis, R. Pacheco-Costa, E.G. Atkinson, L.R. Brun, A.R. Gortazar, J. Harris, M. Hiasa, S.A. Bolarinwa, T. Yoneda, M. Ivan, A. Bruzzaniti, T. Bellido, L.I. Plotkin, Disruption of the Cx43/miR21 pathway leads to osteocyte apoptosis and increased osteoclastogenesis with aging, Aging Cell 16 (3) (2017) 551–563.eng
dcterms.referencesL.F. Bonewald, Establishment and characterization of an osteocyte-like cell line, MLO-Y4, J. Bone Miner. Metab. 17 (1) (1999) 61–65.eng
dcterms.referencesM.K. Sutherland, J.C. Geoghegan, C. Yu, E. Turcott, J.E. Skonier, D.G. Winkler, J.A. Latham, Sclerostin promotes the apoptosis of human osteoblastic cells: a novel regulation of bone formation, Bone 35 (4) (2004) 828–835.eng
dcterms.referencesM.M. McDonald, A. Morse, A. Schindeler, K. Mikulec, L. Peacock, T. Cheng, J. Bobyn, L. Lee, P.A. Baldock, P.I. Croucher, P.P.L. Tam, D.G. Little, Homozygous Dkk1 knockout mice exhibit high bone mass phenotype due to increased bone formation, Calcif. Tissue Int. 102 (1) (2018) 105–116.eng
dcterms.referencesL.I. Plotkin, R.S. Weinstein, A.M. Parfitt, P.K. Roberson, S.C. Manolagas, T. Bellido, Prevention of osteocyte and osteoblast apoptosis by bisphosphonates and calcitonin, J. Clin. Invest. 104 (10) (1999) 1363–1374.eng
dcterms.referencesM. Almeida, L. Han, M. Martin-Millan, L.I. Plotkin, S.A. Stewart, P.K. Roberson, S. Kousteni, C.A. O'Brien, T. Bellido, A.M. Parfitt, R.S. Weinstein, R.L. Jilka, S.C. Manolagas, Skeletal involution by age-associated oxidative stress and its acceleration by loss of sex steroids, J. Biol. Chem. 282 (37) (2007) 27285–27297.eng
dcterms.referencesR.S. Weinstein, R.L. Jilka, A.M. Parfitt, S.C. Manolagas, Inhibition of osteoblastogenesis and promotion of apoptosis of osteoblasts and osteocytes by glucocorticoids. Potential mechanisms of their deleterious effects on bone, J. Clin. Invest. 102 (2) (1998) 274–282.eng
dcterms.referencesO. Verborgt, G.J. Gibson, M.B. Schaffler, Loss of osteocyte integrity in association with microdamage and bone remodeling after fatigue in vivo, J. Bone Miner. Res. Off. J. Am. Soc. Bone Miner. Res. 15 (1) (2000) 60–67.eng
dcterms.referencesR. Deshimaru, K. Ishitani, K. Makita, F. Horiguchi, S. Nozawa, Analysis of fatty acid composition in human bone marrow aspirates, The Keio journal of medicine 54 (3) (2005) 150–155.eng
dcterms.referencesJ.F. Griffith, D.K. Yeung, A.T. Ahuja, C.W. Choy, W.Y. Mei, S.S. Lam, T.P. Lam, Z.Y. Chen, P.C. Leung, A study of bone marrow and subcutaneous fatty acid composition in subjects of varying bone mineral density, Bone 44 (6) (2009) 1092–1096.eng
dcterms.referencesY. Tsujimoto, S. Shimizu, Another way to die: autophagic programmed cell death, Cell Death Differ. 12 (Suppl. 2) (2005) 1528–1534.eng
dcterms.referencesY.S. Rajawat, Z. Hilioti, I. Bossis, Aging: central role for autophagy and the lysosomal degradative system, Ageing Res. Rev. 8 (3) (2009) 199–213.eng
dcterms.referencesF. Madeo, N. Tavernarakis, G. Kroemer, Can autophagy promote longevity? Nat. Cell Biol. 12 (9) (2010) 842–846.eng
dcterms.referencesV. Pierrefite-Carle, S. Santucci-Darmanin, V. Breuil, O. Camuzard, G.F. Carle, Autophagy in bone: self-eating to stay in balance, Ageing Res. Rev. 24 (Pt B) (2015) 206–217.eng
dcterms.referencesM. Onal, M. Piemontese, J. Xiong, Y. Wang, L. Han, S. Ye, M. Komatsu, M. Selig, R.S. Weinstein, H. Zhao, R.L. Jilka, M. Almeida, S.C. Manolagas, C.A. O'Brien, Suppression of autophagy in osteocytes mimics skeletal aging, J. Biol. Chem. 288 (24) (2013) 17432–17440.eng

Ficheros en el ítem


No hay ficheros asociados a este ítem.

Este ítem aparece en la(s) siguiente(s) colección(ones)

  • Artículos
    Artículos científicos evaluados por pares

Mostrar el registro sencillo del ítem

Attribution-NonCommercial-NoDerivatives 4.0 Internacional
Excepto si se señala otra cosa, la licencia del ítem se describe como Attribution-NonCommercial-NoDerivatives 4.0 Internacional