title: The omega-6 arachidonic fatty acid, but not the omega-3 fatty acids, inhibits osteoblastogenesis and induces adipogenesis of human mesenchymal stem cells: potential implication in osteoporosis.
abstract: Arachidonic fatty acid (AA) induces adipogenesis in human mesenchymal stem cells cultures, and high concentrations inhibit osteoblastogenesis; whereas eicosapentaenoic and docosahexaenoic fatty acids do not induce adipogenesis and do not inhibit osteoblastogenesis. In mesenchymal stem cells, omega-6 arachidonic polyunsaturated fatty acid promotes the differentiation of adipocytes and inhibits the osteoblast differentiation. While omega-3 fatty acids do not affect the adipogenic differentiation their effects on osteoblastogenesis are less relevant. An increased ratio of omega-3/omega-6 fatty acid consumption can prevent bone mass loss.
  
  
  BACKGROUND
  Consumption of omega-3 may protect against osteoporosis since they may inhibit osteoclastogenesis. However, with aging, MSC in bone marrow are increasingly differentiated into adipocytes, reducing the number of osteoblasts. Products derived from omega-6 and omega-3 metabolism may affect MSC differentiation into osteoblasts and adipocytes.
  
  
  METHODS
  Human MSC have been differentiated into osteoblasts or adipocytes in the presence of omega-6 (AA), or omega-3 (DHA and EPA), and osteoblastic and adipocytic markers have been analyzed.
  
  
  RESULTS
  AA decreases the expression of osteogenic markers and the osteoprotegerin/receptor activator of nuclear factor kappa β ligand gene expression ratio (opg/rankl). High concentrations of AA inhibit the mineralization and cause the appearance of adipocytes in MSC differentiating into osteoblasts to a higher extent than DHA or EPA. In MSC differentiated into adipocytes, AA increases adipogenesis, while DHA and EPA do not affect it. AA caused the appearance of adipocytes in undifferentiated MSC. The lipoxygenase gene (alox15b) is induced by omega-3 in MSC induced to osteoblasts, and by omega-6 in MSC induced to adipocytes.
  
  
  CONCLUSIONS
  An increase in the intake of omega-3 respect to omega-6 may provide protection against the loss of bone mass, since omega-6 favors the osteoclastic activity by diminishing the opg/rankl gene expression in osteoblasts and promotes MSC differentiation into adipocytes, thus diminishing the production of osteoblasts.
authors.affiliation: Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Hospital Universitario Reina Sofía, RETICEF, Avda. Menéndez Pidal s/n, 14004 Córdoba, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Casado-Díaz
authors.forename: R
authors.initials: R
authors.lastname: Santiago-Mora
authors.forename: G
authors.initials: G
authors.lastname: Dorado
authors.forename: J M
authors.initials: JM
authors.lastname: Quesada-Gómez
mesh_terms: D017667:Adipocytes / Q000166:cytology / Q000187:drug effects; D050156:Adipogenesis / Q000187:drug effects* / Q000502:physiology; D000293:Adolescent; D000328:Adult; D016718:Arachidonic Acid / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology*; D043371:Fatty Acids, Omega-6 / Q000494:pharmacology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006801:Humans; D008084:Lipoxygenase / Q000096:biosynthesis / Q000235:genetics; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects*; D010012:Osteogenesis / Q000187:drug effects / Q000502:physiology; D010024:Osteoporosis / Q000473:pathology / Q000503:physiopathology; D053245:RANK Ligand / Q000235:genetics / Q000378:metabolism; D055815:Young Adult
chemical_list: D015525:Fatty Acids, Omega-3; D043371:Fatty Acids, Omega-6; D053245:RANK Ligand; C505688:TNFSF11 protein, human; D016718:Arachidonic Acid; D008084:Lipoxygenase