Anabolic action of parathyroid hormone is skeletal site specific at the tissue and cellular levels in mice

被引:128
作者
Iida-Klein, A
Zhou, H
Lu, SS
Levine, LR
Ducayen-Knowles, M
Dempster, DW
Nieves, J
Lindsay, R
机构
[1] Helen Hayes Hosp, Reg Bone Ctr, New York State Dept Hlth, W Haverstraw, NY 10993 USA
[2] Columbia Univ, Coll Phys & Surg, Dept Clin Pathol, New York, NY USA
[3] Helen Hayes Hosp, Clin Res Ctr, New York State Dept Hlth, W Haverstraw, NY 10993 USA
[4] Columbia Univ, Coll Phys & Surg, Dept Epidemiol, New York, NY USA
[5] Columbia Univ, Coll Phys & Surg, Dept Med, New York, NY USA
关键词
parathyroid hormone; anabolic actions; bone mineral density; skeletal site specificity; mouse;
D O I
10.1359/jbmr.2002.17.5.808
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
The cellular and molecular events triggering the anabolic response of the skeleton to exogenous parathyroid hormone (PTH) are not well understood. Despite the numerous bone mass studies in rats, few data are available for mice. Therefore, we treated 10-week-old female intact C57BL/6J mice with human PTH(1-34) delivered subcutaneously at a dose of 40 mug/kg per day 5 days a week for 3 weeks and 7 weeks. Bone mineral density (BMD) of total bone, femur, tibia, and lumbar vertebrae was measured weekly by PIXImus. Bone turnover was examined by histomorphometry, and gene expression of bone formation and resorption markers and osteoclastogenesis regulators in the excised femur and tibia was assessed by reverse-transcription polymerase chain reaction (RT-PCR) at 3 weeks and 7 weeks. The PTH-stimulated increase in BMD was more prominent in the tibia and femur than in the lumbar vertebrae, with an anabolic effect detected within 1-2 weeks and BMD continuing to increase. The appearance of a detectable PTH-stimulated increase in BMD was slower in the lumbar vertebrae where the increase was only significant after 7 weeks of treatment. Histomorphometric analysis of the proximal tibia at both 3 weeks and 7 weeks indicated significant time-dependent increases in trabecular area, trabecular number, trabecular and cortical widths, and osteoblast and osteoid perimeters. In the lumbar vertebrae, these stimulatory effects of PTH on trabecular area, trabecular number, and cortical width were smaller and not detected until 7 weeks. PTH-stimulated increases in bone turnover were evident by increased gene expression of osteocalcin (OC), tartrate-resistant acid phosphatase (TRAP), and receptor of activator nuclear factor kappaB (NF-kappaB) ligand (RANKL) in the tibia and femur. No significant difference in gene expression was observed between the two long bone sites. In conclusion, PTH exerts an anabolic action at the tissue and cellular levels in intact mice and the magnitude and temporal pattern of this anabolic action, as assessed by densitometry and histomorphometry, are skeletal site specific.
引用
收藏
页码:808 / 816
页数:9
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