期刊
JOURNAL OF BONE AND MINERAL RESEARCH
卷 23, 期 10, 页码 1672-1679出版社
WILEY
DOI: 10.1359/JBMR.080513
关键词
PTH; hyperlipidemia; BMD; osteoanabolism; mice
资金
- National Institutes of Health [DK076009-01, HL081202]
Epidemiological and in vitro studies have suggested that hyperlipidemia/oxidized phospholipids adversely affect bone. We recently found that oxidized phospholipids attenuate PTH-induced cAMP and immediate-early gene (IEG) expression in MC3T3-E1 cells, raising concerns that clinical hyperlipidemia may attenuate osteoanabolic effects of PTH in vivo. Thus, we studied whether intermittent PTH treatment has differential osteoanabolic effects in wildtype (C57BL/6) and hyperlipidemic (LDLR-/-) mice. Consistent with our previous in vitro studies, induction of IEGs in calvarial tissue, 45 min after a single dose of recombinant hPTH(1-34), was attenuated in LDLR-/- mice compared with C57BL/6 mice. Daily hPTH (1-34) injections for 5 wk significantly increased total and cortical BMD and BMC, assessed by pQCT, in C57BL/6 mice. However, this induction was completely abrogated in LDLR-/- mice. Similarly, PTH(1-34) failed to increase BMD in another hyperlipidemic mouse model, ApoE(-/-) mice. Histomorphometric analysis showed that trabecular bone of both mice responded similarly to PTH(1-34). Structural parameters improved significantly in response to PTH(1-34) in both mouse strains, although to a lesser degree in LDLR-/- mice. With PTH(1-34) treatment, osteoblast surface trended toward an increase in C57BL/6 mice and increased significantly in LDLR-/- mice. PTH(1-34) did not alter resorption parameters significantly, except for the eroded surface (ES/BS), which was reduced in the C57BL/6 but not in the LDLR-/- mice. These results show that PTH(1-34) has adverse effects on cortical bones of the hyperlipidemic mice, suggesting that the therapeutic effects of PTH may be compromised in the presence of hyperlipidemia.
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