Bone resorption induced by parathyroid hormone is strikingly diminished in collagenase-resistant mutant mice

被引:146
作者
Zhao, WG
Byrne, MH
Boyce, BF
Krane, SM
机构
[1] Harvard Univ, Sch Med, Massachusetts Gen Hosp,Dept Med, Med Serv,Arthritis Unit, Boston, MA 02114 USA
[2] Univ Texas, Hlth Sci Ctr, Dept Pathol, San Antonio, TX 78284 USA
关键词
D O I
10.1172/JCI5481
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Parathyroid hormone (PTH) stimulates bone resorption by acting directly on osteoblasts/stromal cells and then indirectly to increase differentiation and function of osteoclasts. PTH acting on osteoblasts/stromal cells increases collagenase gene transcription and synthesis. To assess the role of collagenase in the bone resorptive actions of PTH, we used mice homozygous (r/r) for a targeted mutation (r) in Col1a1 that are resistant to collagenase cleavage of type I collagen. Human PTH(1-34) was injected subcutaneously over the hemicalvariae in wild-type (+/+) or r/r mice four times daily for three days. Osteoclast numbers, the size of the bone marrow spaces and periosteal proliferation were increased in calvariae from PTH-treated +/+ mice, whereas in r/r mice, PTH-induced bone resorption responses were minimal. The r/r mice were not resistant to other skeletal effects of PTH because abundant interstitial collagenase mRNA was detected in the calvarial periosteum of PTH-treated, but not vehicle-treated, r/r and +/+ mice. Calcemic responses, 0.5-10 hours after intraperitoneal injection of PTH, were blunted in r/r mice versus +/+ mice. Thus, collagenase cleavage of type I collagen is necessary for PTH induction of osteoclastic bone resorption.
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页码:517 / 524
页数:8
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