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Glucocorticoids activate the local renin-angiotensin system in bone: possible mechanism for glucocorticoid-induced osteoporosis.

Abstract：

:Bone metabolism disorder has been identified to play a vital role in the pathogenesis of glucocorticoid-induced osteoporosis (GIOP). The local renin-angiotensin system (RAS) in bone is newly defined to be closely related to the bone metabolism. However, it is unknown whether the local RAS is involved in GIOP. Adult male New Zealand white rabbits were treated with saline, dexamethasone (DXM) alone, or DXM combined with perindopril. The expression of main RAS components in trabecular bone was examined at mRNA and/or protein levels. Bone metabolism was analyzed using dual-energy X-ray absorptiometry, histomorphometry, biomechanics, biochemical techniques, and quantitative RT-PCR. The expressions of local bone angiotensin II, angiotensin types 1 and 2 receptors, and angiotensin-converting enzyme at mRNA and/or protein levels increased when DXM-induced osteoporosis was present. Whereas, perindopril significantly blocked the activation of the local RAS and partially reversed GIOP. Mineralizing surface, mineral apposition rate, and bone formation rate were decreased by DXM, along with serum osteocalcin being downregulated. These changes were then reversed by the use of perindopril. Osteoclast number, osteoclast surface, and eroded surface increased after the administration of DXM, and urinary deoxypyridinoline was upregulated. These were also inhibited when perindopril was given. Quantitative RT-PCR using RNA isolated from the lumbar vertebrae revealed an increase in the SOST expression and a decrease in the Runx2 expression, whereas the receptor activator of nuclear factor-κB ligand/osteoprotegerin ratio and the expression of tartrate resistant acid phosphatase were increased, which were all inhibited by perindopril. The results of this study provide evidence for the role of local RAS is involved in GIOP, and GIOP may be ameliorated by blocking the activation of local RAS in the bone.

journal_name

Endocrine

journal_title

Endocrine

authors

Yongtao Z,Kunzheng W,Jingjing Z,Hu S,Jianqiang K,Ruiyu L,Chunsheng W

doi

10.1007/s12020-014-0196-z

subject

Has Abstract

pub_date

2014-11-01 00:00:00

pages

598-608

issue

eissn

1355-008X

issn

1559-0100

journal_volume

pub_type

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Glucocorticoids activate the local renin-angiotensin system in bone: possible mechanism for glucocorticoid-induced osteoporosis.