共 21 条
Pregnancy-associated plasma protein-A modulates the anabolic effects of parathyroid hormone in mouse bone
被引:6
作者:
Clifton, Kari B.
[1
]
Conover, Cheryl A.
[1
]
机构:
[1] Mayo Clin, Div Endocrinol, Rochester, MN 55905 USA
来源:
关键词:
Pregnancy-associated plasma protein-A;
Parathyroid hormone;
Insulin-like growth factor;
Insulin-like growth factor binding proteins;
GROWTH-FACTOR-I;
IGF-I;
BINDING-PROTEIN;
MICE;
RESISTANCE;
DELETION;
RECEPTOR;
D O I:
10.1016/j.bone.2015.08.015
中图分类号:
R5 [内科学];
学科分类号:
1002 ;
100201 ;
摘要:
Intermittent parathyroid hormone (PTH) is a potent anabolic therapy for bone, and several studies have implicated local insulin-like growth factor (IGF) signaling in mediating this effect The IGF system is complex and includes ligands and receptors, as well as IGF binding proteins (IGFBPs) and IGFBP proteases. Pregnancy-associated plasma protein-A (PAPP-A) is a metalloprotease expressed by osteoblasts in vitro that has been shown to enhance local IGF action through cleavage of inhibitory IGFBP-4. This study was set up to test two specific hypotheses: 1) Intermittent PTH treatment increases the expression of IGF-I, IGFBP-4 and PAPP-A in bone in vivo, thereby increasing local IGF activity. 2) In the absence of PAPP-A, local IGF activity and the anabolic effects of PTH on bone are reduced. Wild-type (WT) and PAPP-A knock-out (KO) mice were treated with 80 mu g/kg human PTH 1-34 or vehicle by subcutaneous injection five days per week for six weeks. IGF-I, IGFBP-4 and PAPP-A mRNA expression in bone were significantly increased in response to PTH treatment PTH treatment of WT mice, but not PAPP-A KO mice, significantly increased expression of an IGF-responsive gene. Bone mineral density (BMD), as measured by DEXA, was significantly decreased in femurs of PAPP-A KO compared to WT mice with PTH treatment. Volumetric BMD, as measured by pQCT, was significantly decreased in femoral midshaft (primarily cortical bone), but not metaphysis (primarily trabecular bone), of PAPP-A KO compared to WT mice with PTH treatment These data suggest that stimulation of PAPP-A expression by intermittent PTH treatment contributes to PTH bone anabolism in mice. (C) 2015 Elsevier Inc. All rights reserved.
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页码:413 / 416
页数:4
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