Divergent effects of selective peroxisome proliferator-activated receptor-gamma 2 ligands on adipocyte versus osteoblast differentiation - PubMed (original) (raw)
Comparative Study
. 2002 Jun;143(6):2376-84.
doi: 10.1210/endo.143.6.8834.
Affiliations
- PMID: 12021203
- DOI: 10.1210/endo.143.6.8834
Comparative Study
Divergent effects of selective peroxisome proliferator-activated receptor-gamma 2 ligands on adipocyte versus osteoblast differentiation
Beata Lecka-Czernik et al. Endocrinology. 2002 Jun.
Abstract
PPAR gamma is activated by diverse ligands and regulates the differentiation of many cell types. Based on evidence that activation of PPAR gamma 2 by rosiglitazone stimulates adipogenesis and inhibits osteoblastogenesis in U-33/gamma 2 cells, a model mesenchymal progenitor of adipocytes and osteoblasts, we postulated that the increase in marrow fat and the decrease in osteoblast number that occur during aging are due to increased PPAR gamma 2 activation. Here, we show that the naturally occurring PPAR gamma ligands 9,10-dihydroxyoctadecenoic acid, and 15-deoxy-Delta(12,14)-PGJ(2), also stimulate adipocytes and inhibit osteoblast differentiation of U-33/gamma 2 cells. Strikingly, 9,10-epoxyoctadecenoic acid and the thiazolidine acetamide ligand GW0072 [(+/-)-(2S,5S)-4-(4-(4-carboxyphenyl)butyl)-2-heptyl-4-oxo-5-thaizolidineN,N-dibenzyl-acetamide] prevent osteoblast differentiation, but do not stimulate adipogenesis, whereas 9-hydroxyoctadecadienoic acid stimulates adipogenesis but does not affect osteoblast differentiation. The divergent effects of PPAR gamma 2 ligands on osteoblast and adipocyte differentiation were confirmed in primary murine bone marrow cultures using rosiglitazone and GW0072. These findings indicate that the proadipogenic and antiosteoblastogenic effects of PPAR gamma 2 are mediated by distinct regulatory pathways that can be differentially modulated depending on the nature of the ligand, and they support the idea that increased fatty acid oxidation during aging may inhibit osteoblast differentiation. Moreover, there may be selective PPAR gamma 2 modulators that block the adverse effects of fatty acid oxidation products while retaining beneficial activities such as insulin sensitization.
Similar articles
- Rosiglitazone causes bone loss in mice by suppressing osteoblast differentiation and bone formation.
Ali AA, Weinstein RS, Stewart SA, Parfitt AM, Manolagas SC, Jilka RL. Ali AA, et al. Endocrinology. 2005 Mar;146(3):1226-35. doi: 10.1210/en.2004-0735. Epub 2004 Dec 9. Endocrinology. 2005. PMID: 15591153 - Netoglitazone is a PPAR-gamma ligand with selective effects on bone and fat.
Lazarenko OP, Rzonca SO, Suva LJ, Lecka-Czernik B. Lazarenko OP, et al. Bone. 2006 Jan;38(1):74-84. doi: 10.1016/j.bone.2005.07.008. Epub 2005 Aug 30. Bone. 2006. PMID: 16137931 Free PMC article. - Activation of peroxisome proliferator-activated receptor-gamma inhibits differentiation of preosteoblasts.
Khan E, Abu-Amer Y. Khan E, et al. J Lab Clin Med. 2003 Jul;142(1):29-34. doi: 10.1016/S0022-2143(03)00058-1. J Lab Clin Med. 2003. PMID: 12878983 - Controlling the balance between osteoblastogenesis and adipogenesis and the consequent therapeutic implications.
Nuttall ME, Gimble JM. Nuttall ME, et al. Curr Opin Pharmacol. 2004 Jun;4(3):290-4. doi: 10.1016/j.coph.2004.03.002. Curr Opin Pharmacol. 2004. PMID: 15140422 Review. - Peroxisome proliferator-activated receptor gamma in diabetes and metabolism.
Rangwala SM, Lazar MA. Rangwala SM, et al. Trends Pharmacol Sci. 2004 Jun;25(6):331-6. doi: 10.1016/j.tips.2004.03.012. Trends Pharmacol Sci. 2004. PMID: 15165749 Review.
Cited by
- Integration of texture analysis based on DCE-MRI Ktrans map and metabolomics of early bone marrow microvascular changes in alloxan-induced diabetic rabbits.
Wang Y, Li L, Yan Y, Zhang T, Hu L, Chen J, Zha Y. Wang Y, et al. BMC Med Imaging. 2024 Sep 16;24(1):247. doi: 10.1186/s12880-024-01416-z. BMC Med Imaging. 2024. PMID: 39285283 Free PMC article. - Interrelationships among metabolic syndrome, bone-derived cytokines, and the most common metabolic syndrome-related diseases negatively affecting bone quality.
Martiniakova M, Mondockova V, Kovacova V, Babikova M, Zemanova N, Biro R, Penzes N, Omelka R. Martiniakova M, et al. Diabetol Metab Syndr. 2024 Sep 6;16(1):217. doi: 10.1186/s13098-024-01440-7. Diabetol Metab Syndr. 2024. PMID: 39238022 Free PMC article. Review. - Linoleic acid blunts early osteoblast differentiation and impairs oxidative phosphorylation in vitro.
Nesbeth PC, Ziegler TR, Tripathi AK, Dabeer S, Weiss D, Hao L, Smith MR, Jones DP, Maner-Smith KM, Tu CL, Chang W, Weitzmann MN, Alvarez JA. Nesbeth PC, et al. Prostaglandins Leukot Essent Fatty Acids. 2024 Feb;201:102617. doi: 10.1016/j.plefa.2024.102617. Epub 2024 May 9. Prostaglandins Leukot Essent Fatty Acids. 2024. PMID: 38788347 - The Untargeted Metabolomics Reveals Differences in Energy Metabolism in Patients with Different Subtypes of Ischemic Stroke.
Li X, Li J, Yu F, Feng X, Luo Y, Liu Z, Zhao T, Xia J. Li X, et al. Mol Neurobiol. 2024 Aug;61(8):5308-5319. doi: 10.1007/s12035-023-03884-w. Epub 2024 Jan 6. Mol Neurobiol. 2024. PMID: 38183570 - Time-of-day-dependent variation of the human liver transcriptome and metabolome is disrupted in MASLD.
Johanns M, Haas JT, Raverdy V, Vandel J, Chevalier-Dubois J, Guille L, Derudas B, Legendre B, Caiazzo R, Verkindt H, Gnemmi V, Leteurtre E, Derhourhi M, Bonnefond A, Froguel P, Eeckhoute J, Lassailly G, Mathurin P, Pattou F, Staels B, Lefebvre P. Johanns M, et al. JHEP Rep. 2023 Oct 27;6(1):100948. doi: 10.1016/j.jhepr.2023.100948. eCollection 2024 Jan. JHEP Rep. 2023. PMID: 38125300 Free PMC article.
Publication types
MeSH terms
Substances
Grants and funding
- P01-AG-13918/AG/NIA NIH HHS/United States
- R01-AG-17482/AG/NIA NIH HHS/United States
- R01-AR-46823/AR/NIAMS NIH HHS/United States
- R01-GM-56708/GM/NIGMS NIH HHS/United States
- R03-AG-15605/AG/NIA NIH HHS/United States
LinkOut - more resources
Full Text Sources
Other Literature Sources