| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Division of Endocrinology & Metabolism, Center for Osteoporosis and Metabolic Bone Diseases, Central Arkansas Veterans Healthcare System, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205
Address all correspondence and requests for reprints to: Robert L. Jilka, Ph.D., Division of Endocrinology and Metabolism, Slot 587, University of Arkansas for Medical Sciences, 4301 West Markham, Little Rock, Arkansas 72205. E-mail: jilkarobertl{at}uams.edu.
Because osteoblasts and marrow adipocytes are derived from a common mesenchymal progenitor, increased adipogenesis may occur at the expense of osteoblasts, leading to bone loss. Our previous in vitro studies indicated that activation of the proadipogenic transcription factor peroxisome proliferator-activated receptor isoform 
2 with rosiglitazone suppressed osteoblast differentiation. Here, we show that 5-month-old Swiss-Webster mice receiving rosiglitazone for 28 d exhibited bone loss associated with an increase in marrow adipocytes, a decrease in the ratio of osteoblasts to osteoclasts, a reduction in bone formation rate, and a reduction in wall width—an index of the amount of bone formed by each team of osteoblasts. Rosiglitazone had no effect on the number of early osteoblast or osteoclast progenitors, or on osteoblast life span, but decreased the expression of the key osteoblastogenic transcription factors Runx2 and Osterix in cultures of marrow-derived mesenchymal progenitors. These effects were associated with diversion of bipotential progenitors from the osteoblast to the adipocyte lineage, and suppression of the differentiation of monopotential osteoblast progenitors. However, rosiglitazone had no effect on osteoblastic cells at later stages of differentiation. Hence, rosiglitazone attenuates osteoblast differentiation and thereby reduces bone formation rate in vivo, leading to bone loss. These findings provide a mechanistic explanation for the recent evidence that peroxisome proliferator-activated receptor isoform activation is a negative regulator of bone mass and suggest that the increased production of oxidized fatty acids with age may indeed be an important mechanism for age-related osteoporosis in humans.
This article has been cited by other articles:
 |
|
 |
|
  S. C. Manolagas De-fense! De-fense! De-fense: Scavenging H2O2 While Making Cholesterol Endocrinology, July 1, 2008; 149(7): 3264 - 3266. [Full Text] [PDF]
|
|
|
|
 |
|
 N. Panupinthu, J. T. Rogers, L. Zhao, L. P. Solano-Flores, F. Possmayer, S. M. Sims, and S. J. Dixon P2X7 receptors on osteoblasts couple to production of lysophosphatidic acid: a signaling axis promoting osteogenesis J. Cell Biol., May 28, 2008; 181(5): 859 - 871. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Glintborg, M. Andersen, C. Hagen, L. Heickendorff, and A. P. Hermann Association of Pioglitazone Treatment with Decreased Bone Mineral Density in Obese Premenopausal Patients with Polycystic Ovary Syndrome: A Randomized, Placebo-Controlled Trial J. Clin. Endocrinol. Metab., May 1, 2008; 93(5): 1696 - 1701. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. E. Kahn, B. Zinman, J. M. Lachin, S. M. Haffner, W. H. Herman, R. R. Holman, B. G. Kravitz, D. Yu, M. A. Heise, R. P. Aftring, et al. Rosiglitazone-Associated Fractures in Type 2 Diabetes: An analysis from A Diabetes Outcome Progression Trial (ADOPT) Diabetes Care, May 1, 2008; 31(5): 845 - 851. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Meier, M. E. Kraenzlin, M. Bodmer, S. S. Jick, H. Jick, and C. R. Meier Use of Thiazolidinediones and Fracture Risk Arch Intern Med, April 28, 2008; 168(8): 820 - 825. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Miyawaki, S. Kamei, K. Sakayama, H. Yamamoto, and H. Masuno 4-Tert-Octylphenol Regulates the Differentiation of C3H10T1/2 Cells into Osteoblast and Adipocyte Lineages Toxicol. Sci., March 1, 2008; 102(1): 82 - 88. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. A. Johnson, W. Yao, N. E. Lane, P. Naquet, and R. A. Terkeltaub Vanin-1 Pantetheinase Drives Increased Chondrogenic Potential of Mesenchymal Precursors in ank/ank Mice Am. J. Pathol., February 1, 2008; 172(2): 440 - 453. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. E Murphy and P. T Rodgers Effects of Thiazolidinediones on Bone Loss and Fracture Ann. Pharmacother., December 1, 2007; 41(12): 2014 - 2018. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Berberoglu, A. Gursoy, N. Bayraktar, A. C. Yazici, N. Bascil Tutuncu, and N. Guvener Demirag Rosiglitazone Decreases Serum Bone-Specific Alkaline Phosphatase Activity in Postmenopausal Diabetic Women J. Clin. Endocrinol. Metab., September 1, 2007; 92(9): 3523 - 3530. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. C. Chuang, R. S. Yang, K. S. Tsai, F. M. Ho, and S. H. Liu Hyperglycemia Enhances Adipogenic Induction of Lipid Accumulation: Involvement of Extracellular Signal-Regulated Protein Kinase 1/2, Phosphoinositide 3-Kinase/Akt, and Peroxisome Proliferator-Activated Receptor {gamma} Signaling Endocrinology, September 1, 2007; 148(9): 4267 - 4275. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. V. Schwartz and D. E. Sellmeyer Thiazolidinedione Therapy Gets Complicated: Is bone loss the price of improved insulin resistance? Diabetes Care, June 1, 2007; 30(6): 1670 - 1671. [Full Text] [PDF]
|
|
|
|
|
|
O. P. Lazarenko, S. O. Rzonca, W. R. Hogue, F. L. Swain, L. J. Suva, and B. Lecka-Czernik Rosiglitazone Induces Decreases in Bone Mass and Strength that Are Reminiscent of Aged Bone Endocrinology, June 1, 2007; 148(6): 2669 - 2680. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Acuna-Castroviejo A new guest playing with bone and fat Am J Physiol Regulatory Integrative Comp Physiol, June 1, 2007; 292(6): R2206 - R2207. [Full Text] [PDF]
|
|
|
|
|
|
V. David, A. Martin, M.-H. Lafage-Proust, L. Malaval, S. Peyroche, D. B. Jones, L. Vico, and A. Guignandon Mechanical Loading Down-Regulates Peroxisome Proliferator-Activated Receptor {gamma} in Bone Marrow Stromal Cells and Favors Osteoblastogenesis at the Expense of Adipogenesis Endocrinology, May 1, 2007; 148(5): 2553 - 2562. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. V. Schwartz and D. E. Sellmeyer Thiazolidinediones: New Evidence of Bone Loss J. Clin. Endocrinol. Metab., April 1, 2007; 92(4): 1232 - 1234. [Full Text] [PDF]
|
|
|
|
|
|
A. Grey, M. Bolland, G. Gamble, D. Wattie, A. Horne, J. Davidson, and I. R. Reid The Peroxisome Proliferator-Activated Receptor-{gamma} Agonist Rosiglitazone Decreases Bone Formation and Bone Mineral Density in Healthy Postmenopausal Women: A Randomized, Controlled Trial J. Clin. Endocrinol. Metab., April 1, 2007; 92(4): 1305 - 1310. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Vanek and W. E Connor Do n 3 fatty acids prevent osteoporosis? Am. J. Clinical Nutrition, March 1, 2007; 85(3): 647 - 648. [Full Text] [PDF]
|
|
|
|
|
|
B. Lecka-Czernik, C. Ackert-Bicknell, M. L. Adamo, V. Marmolejos, G. A. Churchill, K. R. Shockley, I. R. Reid, A. Grey, and C. J. Rosen Activation of Peroxisome Proliferator-Activated Receptor {gamma} (PPAR{gamma}) by Rosiglitazone Suppresses Components of the Insulin-Like Growth Factor Regulatory System in Vitro and in Vivo Endocrinology, February 1, 2007; 148(2): 903 - 911. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. B. Watts and D. A. D'Alessio Type 2 diabetes, thiazolidinediones: bad to the bone? J. Clin. Endocrinol. Metab., September 1, 2006; 91(9): 3276 - 3278. [Full Text] [PDF]
|
|
|
|
|
|
A. M. Schwab, S. Granholm, E. Persson, B. Wilkes, U. H. Lerner, and H. H. Conaway Stimulation of Resorption in Cultured Mouse Calvarial Bones by Thiazolidinediones Endocrinology, October 1, 2005; 146(10): 4349 - 4361. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Seeman and G. J. Strewler Clinical and Basic Research Papers - February 2005 Selections IBMS BoneKEy, March 1, 2005; 2(3): 1 - 5. [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Endocrinology | Endocrine Reviews | J. Clin. End. & Metab. |
| Molecular Endocrinology | Recent Prog. Horm. Res. | All Endocrine Journals |
