PMID- 25210048 OWN - NLM STAT- MEDLINE DCOM- 20141230 LR - 20181202 IS - 1479-6805 (Electronic) IS - 0022-0795 (Linking) VI - 223 IP - 2 DP - 2014 Nov TI - Thiazolidinedione-induced lipid droplet formation during osteogenic differentiation. PG - 119-32 LID - 10.1530/JOE-14-0425 [doi] AB - Chronic administration of the insulin-sensitising drugs, thiazolidinediones (TZDs), results in low bone mineral density and 'fatty bones'. This is thought to be due, at least in part, to aberrant differentiation of progenitor mesenchymal stem cells (MSCs) away from osteogenesis towards adipogenesis. This study directly compared the effects of rosiglitazone, pioglitazone, and netoglitazone treatment on osteogenesis and adipogenesis in MSCs derived from subcutaneous (SC) or visceral (PV) white adipose tissue. MSCs were isolated from adipose tissue depots of male Wistar rats and characterised using flow cytometry. The effects of TZD treatment on osteogenic and adipogenic differentiation were assessed histologically (day 14) and by quantitative PCR analysis (Ppargamma2 (Pparg2), Ap2 (Fabp4), Adipsin (Adps), Msx2, Collagen I (Col1a1), and Alp) on days 0, 7, and 10. Uniquely, lipid droplet formation and mineralisation were found to occur concurrently in response to TZD treatment during osteogenesis. Compared with SC MSCs, PV MSCs were more prone to lipid accumulation under controlled osteogenic and adipogenic differentiation conditions. This study demonstrated that the extent of lipid accumulation is dependent on the nature of the Ppar ligand and that SC and PV MSCs respond differently to in vitro TZD treatment, suggesting that metabolic status can contribute to the adverse effects associated with TZD treatment. CI - (c) 2014 Society for Endocrinology. FAU - van de Vyver, M AU - van de Vyver M AD - Division of EndocrinologyDepartment of Medicine, Faculty of Medicine and Health Sciences, Stellenbosch University, PO Box 19063, Tygerberg 7505, South Africa. FAU - Andrag, E AU - Andrag E AD - Division of EndocrinologyDepartment of Medicine, Faculty of Medicine and Health Sciences, Stellenbosch University, PO Box 19063, Tygerberg 7505, South Africa. FAU - Cockburn, I L AU - Cockburn IL AD - Division of EndocrinologyDepartment of Medicine, Faculty of Medicine and Health Sciences, Stellenbosch University, PO Box 19063, Tygerberg 7505, South Africa. FAU - Ferris, W F AU - Ferris WF AD - Division of EndocrinologyDepartment of Medicine, Faculty of Medicine and Health Sciences, Stellenbosch University, PO Box 19063, Tygerberg 7505, South Africa wferris@sun.ac.za. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20140910 PL - England TA - J Endocrinol JT - The Journal of endocrinology JID - 0375363 RN - 0 (Thiazolidinediones) SB - IM MH - Adipocytes/drug effects/physiology MH - Adipogenesis/drug effects MH - Animals MH - Cell Differentiation/drug effects MH - Cells, Cultured MH - Lipid Droplets/*drug effects/metabolism MH - Lipid Metabolism/*drug effects MH - Male MH - Mesenchymal Stem Cells/*drug effects/physiology MH - Osteogenesis/*drug effects MH - Rats MH - Rats, Wistar MH - Thiazolidinediones/*pharmacology OTO - NOTNLM OT - mesenchymal stem cells OT - netoglitazone OT - pioglitazone OT - rosiglitazone EDAT- 2014/09/12 06:00 MHDA- 2014/12/31 06:00 CRDT- 2014/09/12 06:00 PHST- 2014/09/12 06:00 [entrez] PHST- 2014/09/12 06:00 [pubmed] PHST- 2014/12/31 06:00 [medline] AID - JOE-14-0425 [pii] AID - 10.1530/JOE-14-0425 [doi] PST - ppublish SO - J Endocrinol. 2014 Nov;223(2):119-32. doi: 10.1530/JOE-14-0425. Epub 2014 Sep 10.