Thiazolidinediones induce osteocyte apoptosis and increase sclerostin expression

作者: G. Mabilleau , A. Mieczkowska , M. E. Edmonds

DOI: 10.1111/J.1464-5491.2010.03048.X

关键词: ThiazolidinedioneRosiglitazoneEndocrinologyMedicineRANKLOsteocyteProgrammed cell deathPioglitazoneTroglitazoneSclerostinInternal medicine

摘要: Diabet. Med. 27, 925–932 (2010) Abstract Aims  Thiazolidinediones (TZDs) are associated with a higher risk of bone fracture in women compared men. The aim the present study was to investigate whether TZDs could influence osteocyte behaviour and contribute skeletal phenotype observed TZD-treated patients. Methods  murine MLO-Y4 cell line used as source osteocytes. These cells were cultured for 24 h 0, 10−8 m, 10−7 m, 10−6 m, 10−5 m or 10−4 m pioglitazone, rosiglitazone troglitazone presence absence 17β-oestradiol. extent apoptosis assessed, expression formation inhibitor sclerostin receptor activator nuclear factor κB ligand (RANKL) also. Results  In 17β-oestradiol, induced dose-dependently even at lowest concentration 10−8 m. Furthermore, but not RANKL significantly increased cultures untreated cultures. 17β-oestradiol reduced TZD-induced also up-regulation. Conclusions  findings therefore raise potential concern using post-menopausal where lack oestrogen would prevent up-regulation may aggravate reduction mass these patients.

参考文章(31)
Dorte Glintborg, Marianne Andersen, Claus Hagen, Lene Heickendorff, Anne Pernille Hermann, None, Association of pioglitazone treatment with decreased bone mineral density in obese premenopausal patients with polycystic ovary syndrome: a randomized, placebo-controlled trial. The Journal of Clinical Endocrinology and Metabolism. ,vol. 93, pp. 1696- 1701 ,(2008) , 10.1210/JC.2007-2249
C. Huber, S. Collishaw, J. R. Mosley, J. Reeve, B. S. Noble, Selective estrogen receptor modulator inhibits osteocyte apoptosis during abrupt estrogen withdrawal: implications for bone quality maintenance. Calcified Tissue International. ,vol. 81, pp. 139- 144 ,(2007) , 10.1007/S00223-007-9049-6
Enrico Lucarelli, Luca Sangiorgi, Veronica Maini, Giovanna Lattanzi, Sandra Marmiroli, Matteo Reggiani, Marina Mordenti, Giuliana Alessandra Gobbi, Francesca Scrimieri, Annarosa Zambon Bertoja, Piero Picci, Troglitazione affects survival of human osteosarcoma cells. International Journal of Cancer. ,vol. 98, pp. 344- 351 ,(2002) , 10.1002/IJC.10203
S. Zhao, Y. Kato, Y. Zhang, S. Harris, S. S. Ahuja, L. F. Bonewald, MLO-Y4 osteocyte-like cells support osteoclast formation and activation. Journal of Bone and Mineral Research. ,vol. 17, pp. 2068- 2079 ,(2002) , 10.1359/JBMR.2002.17.11.2068
Lilian I. Plotkin, J. Ignacio Aguirre, Stavroula Kousteni, Stavros C. Manolagas, Teresita Bellido, Bisphosphonates and estrogens inhibit osteocyte apoptosis via distinct molecular mechanisms downstream of extracellular signal-regulated kinase activation. Journal of Biological Chemistry. ,vol. 280, pp. 7317- 7325 ,(2005) , 10.1074/JBC.M412817200
Hong-Nu Yu, Eun-Mi Noh, Young-Rae Lee, Si-Gyun Roh, Eun-Kyung Song, Myung-Kwan Han, Yong-Chul Lee, In Kyong Shim, Seung Jin Lee, Sung Hoo Jung, Jong-Suk Kim, Hyun Jo Youn, Troglitazone enhances tamoxifen-induced growth inhibitory activity of MCF-7 cells. Biochemical and Biophysical Research Communications. ,vol. 377, pp. 242- 247 ,(2008) , 10.1016/J.BBRC.2008.09.111
Lilian I Plotkin, Virginia Lezcano, Jeff Thostenson, Robert S Weinstein, Stavros C Manolagas, Teresita Bellido, Connexin 43 Is Required for the Anti‐Apoptotic Effect of Bisphosphonates on Osteocytes and Osteoblasts In Vivo Journal of Bone and Mineral Research. ,vol. 23, pp. 1712- 1721 ,(2008) , 10.1359/JBMR.080617
Cristina Vincent, David M Findlay, Katie J Welldon, Asiri R Wijenayaka, Timothy S Zheng, David R Haynes, Nicola L Fazzalari, Andreas Evdokiou, Gerald J Atkins, Pro‐Inflammatory Cytokines TNF‐Related Weak Inducer of Apoptosis (TWEAK) and TNFα Induce the Mitogen‐Activated Protein Kinase (MAPK)‐Dependent Expression of Sclerostin in Human Osteoblasts Journal of Bone and Mineral Research. ,vol. 24, pp. 1434- 1449 ,(2009) , 10.1359/JBMR.090305