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Sphingolipid metabolism and its role in the skeletal tissues

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Abstract

The regulators affecting skeletal tissue formation and its maintenance include a wide array of molecules with very diverse functions. More recently, sphingolipids have been added to this growing list of regulatory molecules in the skeletal tissues. Sphingolipids are integral parts of various lipid membranes present in the cells and organelles. For a long time, these macromolecules were considered as inert structural elements. This view, however, has radically changed in recent years as sphingolipids are now recognized as important second messengers for signal-transduction pathways that affect cell growth, differentiation, stress responses and programmed death. In the current review, we discuss the available data showing the roles of various sphingolipids in three different skeletal cell types—chondrocytes in cartilage and osteoblasts and osteoclasts in bone. We provide an overview of the biology of sphingomyelin phosphodiesterase 3 (SMPD3), an important regulator of sphingolipid metabolism in the skeleton. SMPD3 is localized in the plasma membrane and has been shown to cleave sphingomyelin to generate ceramide, a bioactive lipid second messenger, and phosphocholine, an essential nutrient. SMPD3 deficiency in mice impairs the mineralization in both cartilage and bone extracellular matrices leading to severe skeletal deformities. A detailed understanding of SMPD3 function may provide a novel insight on the role of sphingolipids in the skeletal tissues.

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References

  1. Horton WA, Degnin CR (2009) FGFs in endochondral skeletal development. Trends Endocrinol Metab 20(7):341–348

    Article  CAS  PubMed  Google Scholar 

  2. Karsenty G (2011) Bone endocrine regulation of energy metabolism and male reproduction. C R Biol 334(10):720–724

    Article  CAS  PubMed  Google Scholar 

  3. Karsenty G (2003) The complexities of skeletal biology. Nature 423(6937):316–318

    Article  CAS  PubMed  Google Scholar 

  4. Karsenty G, Kronenberg HM, Settembre C (2009) Genetic control of bone formation. Annu Rev Cell Dev Biol 25:629–648

    Article  CAS  PubMed  Google Scholar 

  5. Mackie EJ, Tatarczuch L, Mirams M (2011) The skeleton: a multi-functional complex organ: the growth plate chondrocyte and endochondral ossification. J Endocrinol 211(2):109–121

    Article  CAS  PubMed  Google Scholar 

  6. Amano K, Hata K, Sugita A, Takigawa Y, Ono K, Wakabayashi M, Kogo M, Nishimura R, Yoneda T (2009) Sox9 family members negatively regulate maturation and calcification of chondrocytes through up-regulation of parathyroid hormone-related protein. Mol Biol Cell 20(21):4541–4551

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  7. Amizuka N, Henderson JE, Hoshi K, Warshawsky H, Ozawa H, Goltzman D, Karaplis AC (1996) Programmed cell death of chondrocytes and aberrant chondrogenesis in mice homozygous for parathyroid hormone-related peptide gene deletion. Endocrinology 137(11):5055–5067

    CAS  PubMed  Google Scholar 

  8. Degnin CR, Laederich MB, Horton WA (2010) FGFs in endochondral skeletal development. J Cell Biochem 110(5):1046–1057

    Article  CAS  PubMed  Google Scholar 

  9. Ducy P, Zhang R, Geoffroy V, Ridall AL, Karsenty G (1997) Osf2/Cbfa1: a transcriptional activator of osteoblast differentiation. Cell 89(5):747–754

    Article  CAS  PubMed  Google Scholar 

  10. Komori T, Yagi H, Nomura S, Yamaguchi A, Sasaki K, Deguchi K, Shimizu Y, Bronson RT, Gao YH, Inada M, Sato M, Okamoto R, Kitamura Y, Yoshiki S, Kishimoto T (1997) Targeted disruption of Cbfa1 results in a complete lack of bone formation owing to maturational arrest of osteoblasts. Cell 89(5):755–764

    Article  CAS  PubMed  Google Scholar 

  11. Kozhemyakina E, Cohen T, Yao TP, Lassar AB (2009) Parathyroid hormone-related peptide represses chondrocyte hypertrophy through a protein phosphatase 2A/histone deacetylase 4/MEF2 pathway. Mol Cell Biol 29(21):5751–5762

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  12. Merrill AH Jr (2002) De novo sphingolipid biosynthesis: a necessary, but dangerous, pathway. J Biol Chem 277(29):25843–25846

    Article  CAS  PubMed  Google Scholar 

  13. Nakashima K, Zhou X, Kunkel G, Zhang Z, Deng JM, Behringer RR, de Crombrugghe B (2002) The novel zinc finger-containing transcription factor osterix is required for osteoblast differentiation and bone formation. Cell 108(1):17–29

    Article  CAS  PubMed  Google Scholar 

  14. Nesbitt T, Fujiwara I, Thomas R, Xiao ZS, Quarles LD, Drezner MK (1999) Coordinated maturational regulation of PHEX and renal phosphate transport inhibitory activity: evidence for the pathophysiological role of PHEX in X-linked hypophosphatemia. J Bone Miner Res 14(12):2027–2035

    Article  CAS  PubMed  Google Scholar 

  15. Ornitz DM, Marie PJ (2002) FGF signaling pathways in endochondral and intramembranous bone development and human genetic disease. Genes Dev 16(12):1446–1465

    Article  CAS  PubMed  Google Scholar 

  16. Retting KN, Song B, Yoon BS, Lyons KM (2009) BMP canonical Smad signaling through Smad1 and Smad5 is required for endochondral bone formation. Development 136(7):1093–1104

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  17. Roberts S, Narisawa S, Harmey D, Millan JL, Farquharson C (2007) Functional involvement of PHOSPHO1 in matrix vesicle-mediated skeletal mineralization. J Bone Miner Res 22(4):617–627

    Article  CAS  PubMed  Google Scholar 

  18. Stewart AJ, Roberts SJ, Seawright E, Davey MG, Fleming RH, Farquharson C (2006) The presence of PHOSPHO1 in matrix vesicles and its developmental expression prior to skeletal mineralization. Bone 39(5):1000–1007

    Article  CAS  PubMed  Google Scholar 

  19. Stonich D, Su Y, Dad S, Reddy S, Mostofi Y, Russell D, Chung TDY, Hedrick NM, Rascon J, Garcia X, Sergienko E, Millan JL, Cosford N 2010 The role of PHOSPHO1 in the initiation of skeletal calcification

  20. Whyte MP (1994) Hypophosphatasia and the role of alkaline phosphatase in skeletal mineralization. Endocr Rev 15(4):439–461

    CAS  PubMed  Google Scholar 

  21. Zhou Z, Xie J, Lee D, Liu Y, Jung J, Zhou L, Xiong S, Mei L, Xiong WC (2010) Neogenin regulation of BMP-induced canonical Smad signaling and endochondral bone formation. Dev Cell 19(1):90–102

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  22. Aubin I, Adams CP, Opsahl S, Septier D, Bishop CE, Auge N, Salvayre R, Negre-Salvayre A, Goldberg M, Guenet JL, Poirier C (2005) A deletion in the gene encoding sphingomyelin phosphodiesterase 3 (Smpd3) results in osteogenesis and dentinogenesis imperfecta in the mouse. Nat Genet 37(8):803–805

    Article  CAS  PubMed  Google Scholar 

  23. Khavandgar Z, Alebrahim S, Eimar H, Tamimi F, McKee MD, Murshed M (2013) Local regulation of tooth mineralization by sphingomyelin phosphodiesterase 3. J Dent Res 92(4):358–364

    Article  CAS  PubMed  Google Scholar 

  24. Khavandgar Z, Poirier C, Clarke CJ, Li J, Wang N, McKee MD, Hannun YA, Murshed M (2011) A cell-autonomous requirement for neutral sphingomyelinase 2 in bone mineralization. J Cell Biol 194(2):277–289

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  25. Stoffel W (1999) Functional analysis of acid and neutral sphingomyelinases in vitro and in vivo. Chem Phys Lipids 102(1–2):107–121

    Article  CAS  PubMed  Google Scholar 

  26. Merrill AH Jr, Schmelz EM, Dillehay DL, Spiegel S, Shayman JA, Schroeder JJ, Riley RT, Voss KA, Wang E (1997) Sphingolipids–the enigmatic lipid class: biochemistry, physiology, and pathophysiology. Toxicol Appl Pharmacol 142(1):208–225

    Article  CAS  PubMed  Google Scholar 

  27. Airola MV, Hannun YA (2013) Sphingolipid metabolism and neutral sphingomyelinases. Handb Exp Pharmacol 215:57–76

    Article  CAS  PubMed  Google Scholar 

  28. Mullen TD, Hannun YA, Obeid LM (2012) Ceramide synthases at the centre of sphingolipid metabolism and biology. Biochem J 441(3):789–802

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  29. Hannun YA, Obeid LM (2011) Many ceramides. J Biol Chem 286(32):27855–27862

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  30. Futerman AH, Riezman H (2005) The ins and outs of sphingolipid synthesis. Trends Cell Biol 15(6):312–318

    Article  CAS  PubMed  Google Scholar 

  31. Nilsson A, Duan RD (1999) Alkaline sphingomyelinases and ceramidases of the gastrointestinal tract. Chem Phys Lipids 102(1–2):97–105

    Article  CAS  PubMed  Google Scholar 

  32. Kirschnek S, Paris F, Weller M, Grassme H, Ferlinz K, Riehle A, Fuks Z, Kolesnick R, Gulbins E (2000) CD95-mediated apoptosis in vivo involves acid sphingomyelinase. J Biol Chem 275(35):27316–27323

    CAS  PubMed  Google Scholar 

  33. Duan RD, Nyberg L, Nilsson A (1995) Alkaline sphingomyelinase activity in rat gastrointestinal tract: distribution and characteristics. Biochim Biophys Acta 1259(1):49–55

    Article  PubMed  Google Scholar 

  34. Duan RD (2006) Alkaline sphingomyelinase: an old enzyme with novel implications. Biochim Biophys Acta 1761(3):281–291

    Article  CAS  PubMed  Google Scholar 

  35. Herr I, Debatin KM (2001) Cellular stress response and apoptosis in cancer therapy. Blood 98(9):2603–2614

    Article  CAS  PubMed  Google Scholar 

  36. Siskind LJ, Kolesnick RN, Colombini M (2006) Ceramide forms channels in mitochondrial outer membranes at physiologically relevant concentrations. Mitochondrion 6(3):118–125

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  37. Chipuk JE, McStay GP, Bharti A, Kuwana T, Clarke CJ, Siskind LJ, Obeid LM, Green DR (2012) Sphingolipid metabolism cooperates with BAK and BAX to promote the mitochondrial pathway of apoptosis. Cell 148(5):988–1000

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  38. Olivier S, Fillet M, Malaise M, Piette J, Bours V, Merville MP, Franchimont N (2005) Sodium nitroprusside-induced osteoblast apoptosis is mediated by long chain ceramide and is decreased by raloxifene. Biochem Pharmacol 69(6):891–901

    Article  CAS  PubMed  Google Scholar 

  39. Snyder CM, Shroff EH, Liu J, Chandel NS (2009) Nitric oxide induces cell death by regulating anti-apoptotic BCL-2 family members. PLoS One 4(9):e7059

    Article  PubMed Central  PubMed  Google Scholar 

  40. Kitajima I, Soejima Y, Takasaki I, Beppu H, Tokioka T, Maruyama I (1996) Ceramide-induced nuclear translocation of NF-kappa B is a potential mediator of the apoptotic response to TNF-alpha in murine clonal osteoblasts. Bone 19(3):263–270

    Article  CAS  PubMed  Google Scholar 

  41. Chae HJ, Chae SW, Kang JS, Bang BG, Cho SB, Park RK, So HS, Kim YK, Kim HM, Kim HR (2000) Dexamethasone suppresses tumor necrosis factor-alpha-induced apoptosis in osteoblasts: possible role for ceramide. Endocrinology 141(8):2904–2913

    CAS  PubMed  Google Scholar 

  42. Hill PA, Tumber A (2010) Ceramide-induced cell death/survival in murine osteoblasts. J Endocrinol 206(2):225–233

    Article  CAS  PubMed  Google Scholar 

  43. Sabatini M, Rolland G, Leonce S, Thomas M, Lesur C, Perez V, de Nanteuil G, Bonnet J (2000) Effects of ceramide on apoptosis, proteoglycan degradation, and matrix metalloproteinase expression in rabbit articular cartilage. Biochem Biophys Res Commun 267(1):438–444

    Article  CAS  PubMed  Google Scholar 

  44. MacRae VE, Burdon T, Ahmed SF, Farquharson C (2006) Ceramide inhibition of chondrocyte proliferation and bone growth is IGF-I independent. J Endocrinol 191(2):369–377

    Article  CAS  PubMed  Google Scholar 

  45. Takeda H, Ozaki K, Yasuda H, Ishida M, Kitano S, Hanazawa S (1998) Sphingomyelinase and ceramide inhibit formation of F-actin ring in and bone resorption by rabbit mature osteoclasts. FEBS Lett 422(2):255–258

    Article  PubMed  Google Scholar 

  46. Lee SE, Chung WJ, Kwak HB, Chung CH, Kwack KB, Lee ZH, Kim HH (2001) Tumor necrosis factor-alpha supports the survival of osteoclasts through the activation of Akt and ERK. J Biol Chem 276(52):49343–49349

    Article  CAS  PubMed  Google Scholar 

  47. Iwamoto T, Fukumoto S, Kanaoka K, Sakai E, Shibata M, Fukumoto E, Inokuchi Ji J, Takamiya K, Furukawa K, Kato Y, Mizuno A (2001) Lactosylceramide is essential for the osteoclastogenesis mediated by macrophage-colony-stimulating factor and receptor activator of nuclear factor-kappa B ligand. J Biol Chem 276(49):46031–46038

    Article  CAS  PubMed  Google Scholar 

  48. Fukumoto S, Iwamoto T, Sakai E, Yuasa K, Fukumoto E, Yamada A, Hasegawa T, Nonaka K, Kato Y (2006) Current topics in pharmacological research on bone metabolism: osteoclast differentiation regulated by glycosphingolipids. J Pharmacol Sci 100(3):195–200

    Article  CAS  PubMed  Google Scholar 

  49. Kato K, Adachi S, Matsushima-Nishiwaki R, Minamitani C, Natsume H, Katagiri Y, Hirose Y, Mizutani J, Tokuda H, Kozawa O, Otsuka T (2011) Regulation by heat shock protein 27 of osteocalcin synthesis in osteoblasts. Endocrinology 152(5):1872–1882

    Article  CAS  PubMed  Google Scholar 

  50. Kozawa O, Niwa M, Matsuno H, Tokuda H, Miwa M, Ito H, Kato K, Uematsu T (1999) Sphingosine 1-phosphate induces heat shock protein 27 via p38 mitogen-activated protein kinase activation in osteoblasts. J Bone Miner Res 14(10):1761–1767

    Article  CAS  PubMed  Google Scholar 

  51. Sato C, Iwasaki T, Kitano S, Tsunemi S, Sano H (2012) Sphingosine 1-phosphate receptor activation enhances BMP-2-induced osteoblast differentiation. Biochem Biophys Res Commun 423(1):200–205

    Article  CAS  PubMed  Google Scholar 

  52. Liu R, Farach-Carson MC, Karin NJ (1995) Effects of sphingosine derivatives on MC3T3-E1 pre-osteoblasts: psychosine elicits release of calcium from intracellular stores. Biochem Biophys Res Commun 214(2):676–684

    Article  CAS  PubMed  Google Scholar 

  53. Lyons JM, Karin NJ (2001) A role for G protein-coupled lysophospholipid receptors in sphingolipid-induced Ca2+ signaling in MC3T3-E1 osteoblastic cells. J Bone Miner Res 16(11):2035–2042

    Article  CAS  PubMed  Google Scholar 

  54. Grey A, Chen Q, Callon K, Xu X, Reid IR, Cornish J (2002) The phospholipids sphingosine-1-phosphate and lysophosphatidic acid prevent apoptosis in osteoblastic cells via a signaling pathway involving G(i) proteins and phosphatidylinositol-3 kinase. Endocrinology 143(12):4755–4763

    Article  CAS  PubMed  Google Scholar 

  55. Roelofsen T, Akkers R, Beumer W, Apotheker M, Steeghs I, van de Ven J, Gelderblom C, Garritsen A, Dechering K (2008) Sphingosine-1-phosphate acts as a developmental stage specific inhibitor of platelet-derived growth factor-induced chemotaxis of osteoblasts. J Cell Biochem 105(4):1128–1138

    Article  CAS  PubMed  Google Scholar 

  56. Quint P, Ruan M, Pederson L, Kassem M, Westendorf JJ, Khosla S, Oursler MJ (2013) Sphingosine 1-phosphate (S1P) receptors 1 and 2 coordinately induce mesenchymal cell migration through S1P activation of complementary kinase pathways. J Biol Chem 288(8):5398–5406

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  57. Kim MK, Lee HY, Kwak JY, Park JI, Yun J, Bae YS (2006) Sphingosine-1-phosphate stimulates rat primary chondrocyte proliferation. Biochem Biophys Res Commun 345(1):67–73

    Article  CAS  PubMed  Google Scholar 

  58. Masuko K, Murata M, Beppu M, Nakamura H, Kato T, Yudoh K (2012) Sphingosine-1-phosphate modulates expression of vascular endothelial growth factor in human articular chondrocytes: a possible new role in arthritis. Int J Rheum Dis 15(4):366–373

    Article  CAS  PubMed  Google Scholar 

  59. Masuko K, Murata M, Nakamura H, Yudoh K, Nishioka K, Kato T (2007) Sphingosine-1-phosphate attenuates proteoglycan aggrecan expression via production of prostaglandin E2 from human articular chondrocytes. BMC Musculoskelet Disord 8:29

    Article  PubMed Central  PubMed  Google Scholar 

  60. Ishii M (1831) Kikuta J 2013 Sphingosine-1-phosphate signaling controlling osteoclasts and bone homeostasis. Biochim Biophys Acta 1:223–227

    Google Scholar 

  61. Lotinun S, Kiviranta R, Matsubara T, Alzate JA, Neff L, Luth A, Koskivirta I, Kleuser B, Vacher J, Vuorio E, Horne WC, Baron R (2013) Osteoclast-specific cathepsin K deletion stimulates S1P-dependent bone formation. J Clin Invest 123(2):666–681

    PubMed Central  CAS  PubMed  Google Scholar 

  62. Keller J, Catala-Lehnen P, Huebner AK, Jeschke A, Heckt T, Lueth A, Krause M, Koehne T, Albers J, Schulze J, Schilling S, Haberland M, Denninger H, Neven M, Hermans-Borgmeyer I, Streichert T, Breer S, Barvencik F, Levkau B, Rathkolb B, Wolf E, Calzada-Wack J, Neff F, Gailus-Durner V, Fuchs H, de Angelis MH, Klutmann S, Tsourdi E, Hofbauer LC, Kleuser B, Chun J, Schinke T, Amling M (2014) Calcitonin controls bone formation by inhibiting the release of sphingosine 1-phosphate from osteoclasts. Nat Commun 21(5), p 5215

    Article  Google Scholar 

  63. Guenet JL, Stanescu R, Maroteaux P, Stanescu V (1981) Fragilitas ossium: a new autosomal recessive mutation in the mouse. J Hered 72(6):440–441

    CAS  PubMed  Google Scholar 

  64. Stoffel W, Jenke B, Block B, Zumbansen M, Koebke J (2005) Neutral sphingomyelinase 2 (smpd3) in the control of postnatal growth and development. Proc Natl Acad Sci USA 102(12):4554–4559

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  65. Stoffel W, Jenke B, Holz B, Binczek E, Gunter RH, Knifka J, Koebke J, Niehoff A (2007) Neutral sphingomyelinase (SMPD3) deficiency causes a novel form of chondrodysplasia and dwarfism that is rescued by Col2A1-driven smpd3 transgene expression. Am J Pathol 171(1):153–161

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  66. Hannun YA, Obeid LM (2002) The Ceramide-centric universe of lipid-mediated cell regulation: stress encounters of the lipid kind. J Biol Chem 277(29):25847–25850

    Article  CAS  PubMed  Google Scholar 

  67. Li Z, Wu G, Sher RB, Khavandgar Z, Hermansson M, Cox GA, Doschak MR, Murshed M, Beier F, Vance DE (2014) Choline kinase beta is required for normal endochondral bone formation. Biochim Biophys Acta 1840(7):2112–2122

    Article  CAS  PubMed  Google Scholar 

  68. Kakoi H, Maeda S, Shinohara N, Matsuyama K, Imamura K, Kawamura I, Nagano S, Setoguchi T, Yokouchi M, Ishidou Y, Komiya S (2014) Bone morphogenic protein (BMP) signaling up-regulates neutral sphingomyelinase 2 to suppress chondrocyte maturation via the Akt protein signaling pathway as a negative feedback mechanism. J Biol Chem 289(12):8135–8150

    Article  CAS  PubMed  Google Scholar 

  69. Holland WL, Brozinick JT, Wang LP, Hawkins ED, Sargent KM, Liu Y, Narra K, Hoehn KL, Knotts TA, Siesky A, Nelson DH, Karathanasis SK, Fontenot GK, Birnbaum MJ, Summers SA (2007) Inhibition of ceramide synthesis ameliorates glucocorticoid-, saturated-fat-, and obesity-induced insulin resistance. Cell Metab 5(3):167–179

    Article  CAS  PubMed  Google Scholar 

  70. Yadav MC, Simao AM, Narisawa S, Huesa C, McKee MD, Farquharson C, Millan JL (2011) Loss of skeletal mineralization by the simultaneous ablation of PHOSPHO1 and alkaline phosphatase function: a unified model of the mechanisms of initiation of skeletal calcification. J Bone Miner Res 26(2):286–297

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  71. Brophy PJ, Choy PC, Toone JR, Vance DE (1977) Choline kinase and ethanolamine kinase are separate, soluble enzymes in rat liver. Eur J Biochem 78(2):491–495

    Article  CAS  PubMed  Google Scholar 

  72. Gallego-Ortega D, Ramirez de Molina A, Ramos MA, Valdes-Mora F, Barderas MG, Sarmentero-Estrada J, Lacal JC (2009) Differential role of human choline kinase alpha and beta enzymes in lipid metabolism: implications in cancer onset and treatment. PLoS One 4(11):e7819

    Article  PubMed Central  PubMed  Google Scholar 

  73. Anderson HC (2003) Matrix vesicles and calcification. Curr Rheumatol Rep 5(3):222–226

    Article  PubMed  Google Scholar 

  74. Wu LN, Genge BR, Kang MW, Arsenault AL, Wuthier RE (2002) Changes in phospholipid extractability and composition accompany mineralization of chicken growth plate cartilage matrix vesicles. J Biol Chem 277(7):5126–5133

    Article  CAS  PubMed  Google Scholar 

  75. Mebarek S, Abousalham A, Magne D, le Do D, Bandorowicz-Pikula J, Pikula S, Buchet R (2013) Phospholipases of mineralization competent cells and matrix vesicles: roles in physiological and pathological mineralizations. Int J Mol Sci 14(3):5036–5129

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  76. Coleman RM, Aguilera L, Quinones L, Lukashova L, Poirier C, Boskey A (2012) Comparison of bone tissue properties in mouse models with collagenous and non-collagenous genetic mutations using FTIRI. Bone 51(5):920–928

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  77. Lipina C, Hundal HS (2011) Sphingolipids: agents provocateurs in the pathogenesis of insulin resistance. Diabetologia 54(7):1596–1607

    Article  CAS  PubMed  Google Scholar 

  78. Samad F, Badeanlou L, Shah C, Yang G (2011) Adipose tissue and ceramide biosynthesis in the pathogenesis of obesity. Adv Exp Med Biol 721:67–86

    Article  CAS  PubMed  Google Scholar 

  79. Yang G, Badeanlou L, Bielawski J, Roberts AJ, Hannun YA, Samad F (2009) Central role of ceramide biosynthesis in body weight regulation, energy metabolism, and the metabolic syndrome. Am J Physiol Endocrinol Metab 297(1):E211–E224

    Article  PubMed Central  CAS  PubMed  Google Scholar 

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  1. Faculty of Dentistry, McGill University, Montreal, Quebec, Canada

    Zohreh Khavandgar & Monzur Murshed

  2. Department of Medicine, McGill University, Montreal, Quebec, Canada

    Monzur Murshed

  3. Shriners Hospital for Children, McGill University, Montreal, Quebec, Canada

    Monzur Murshed

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Khavandgar, Z., Murshed, M. Sphingolipid metabolism and its role in the skeletal tissues. Cell. Mol. Life Sci. 72, 959–969 (2015). https://doi.org/10.1007/s00018-014-1778-x

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