title: Biochemical changes induced by strontium ranelate in differentiating adipocytes.
abstract: Low bone formation in osteoporosis is associated with a shift from osteoblastic to adipogenic differentiation of mesenchymal stem cells (MSC) inducing a concomitant lipotoxic milieu within the bone marrow. Strontium ranelate (SrRN), a treatment for osteoporosis, has both anti-resorptive and anabolic effects on bone. The anabolic effect of SrRN has been associated with its effect on both osteoblastogenesis and adipogenesis. However, the effect of SrRN on the potentially lipotoxic factors produced by differentiating marrow adipocytes remains poorly understood. To expand the knowledge on the effect of SrRN treatment on the bone microenvironment, we assessed changes in adipogenic factors and adipokine expression in adipocytic differentiation of MSC in vitro. Primary human MSC were induced to differentiate in adipogenic conditions in the presence or absence of SrRN (1-2 mM). We tested the dose-dependent effects of SrRN on adipocyte differentiation including changes in the expression of adipogenic markers and adipokines. We report that adipogenesis was negatively affected in the presence of SrRN with a concomitant dose-dependent decrease in the expression of adipogenic markers and changes in adipokine profile. Taken together, our data suggests that SrRN induces biochemical changes in differentiating adipocytes that could generate a favorable osteogenic effect within the bone marrow milieu.
authors.affiliation: Ageing Bone Research Program, Sydney Medical School Nepean, The University of Sydney, Penrith, NSW 2750, Australia. chris.vidal@sydney.edu.au
authors.forename: Christopher
authors.initials: C
authors.lastname: Vidal
authors.forename: Krishanthi
authors.initials: K
authors.lastname: Gunaratnam
authors.forename: Jessica
authors.initials: J
authors.lastname: Tong
authors.forename: Gustavo
authors.initials: G
authors.lastname: Duque
mesh_terms: D017667:Adipocytes / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D050156:Adipogenesis / Q000187:drug effects; D054392:Adipokines / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009942:Organometallic Compounds / Q000494:pharmacology*; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism; D013876:Thiophenes / Q000494:pharmacology*
chemical_list: D054392:Adipokines; D009942:Organometallic Compounds; D047495:PPAR gamma; D013876:Thiophenes; C081587:strontium ranelate