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Thiazolidinediones induce osteocyte apoptosis and increase sclerostin expression
Author(s) -
Mabilleau G.,
Mieczkowska A.,
Edmonds M. E.
Publication year - 2010
Publication title -
diabetic medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.474
H-Index - 145
eISSN - 1464-5491
pISSN - 0742-3071
DOI - 10.1111/j.1464-5491.2010.03048.x
Subject(s) - osteocyte , sclerostin , rankl , endocrinology , medicine , pioglitazone , troglitazone , rosiglitazone , apoptosis , bone remodeling , receptor , osteoblast , peroxisome proliferator activated receptor , chemistry , microbiology and biotechnology , activator (genetics) , biology , signal transduction , wnt signaling pathway , in vitro , biochemistry , type 2 diabetes , diabetes mellitus
Diabet. Med. 27, 925–932 (2010) Abstract Aims  Thiazolidinediones (TZDs) are associated with a higher risk of bone fracture in women compared with men. The aim of the present study was to investigate whether TZDs could influence osteocyte behaviour and contribute to the skeletal phenotype observed in TZD‐treated patients. Methods  The murine MLO‐Y4 cell line was used as a source of osteocytes. These cells were cultured for 24 h with 0, 10 −8   m , 10 −7   m , 10 −6   m , 10 −5   m or 10 −4   m of pioglitazone, rosiglitazone or troglitazone in the presence or absence of 17β‐oestradiol. The extent of osteocyte apoptosis was assessed, as was the expression of the bone formation inhibitor sclerostin and receptor activator for nuclear factor κB ligand (RANKL) also. Results  In the absence of 17β‐oestradiol, pioglitazone, rosiglitazone and troglitazone induced osteocyte apoptosis dose‐dependently even at the lowest concentration of 10 −8   m . Furthermore, the expression of sclerostin but not RANKL was significantly increased in TZD‐treated cultures compared with untreated cultures. The presence of 17β‐oestradiol significantly reduced TZD‐induced osteocyte apoptosis and also sclerostin up‐regulation. Conclusions  These findings therefore raise the potential concern of using TZDs in post‐menopausal women where the lack of oestrogen would not prevent osteocyte apoptosis and sclerostin up‐regulation and may aggravate the reduction in bone mass in these patients.

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