Parathyroid hormone enhances mechanically induced bone formation, possibly involving L-type voltage-sensitive calcium channels
Parathyroid hormone enhances mechanically induced bone formation, possibly involving L-type voltage-sensitive calcium channels
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DOI：
10.1210/en.2002-220821
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发表时间：
2003-04-01
期刊：
影响因子：
4.8
通讯作者：
Turner, CH
中科院分区：
文献类型：
--
作者：
Li, J;Duncan, RL;Turner, CH
PTH和机械负荷可能协同作用于骨形成。我们测试了L型电压敏感性钙通道（VSCC）阻滞剂维拉帕米对人PTH-（1-34）（PTH）注射诱导骨形成的体内作用，有或没有机械负荷。成年大鼠分为8组：溶剂组、维拉帕米组、PTH组或维拉帕米加PTH组（有或无机械负荷）。负荷前90 min口服维拉帕米（100 mg/kg）。负荷前30分钟皮下注射PTH（80 μ g/kg）。胫骨和尺骨负荷3 min可显著增加胫骨皮质内面和尺骨骨膜面的成骨率（P < 0.0001）。PTH治疗使皮质内和骨膜表面的负荷诱导骨形成分别增加了53%和76%（P < 0.001）。维拉帕米治疗组的骨形成率分别降低77%和59%（P < 0.01）。此外，维拉帕米抑制骨形成在大鼠PTH加负荷分别为74%和68%（P< 0.0001）在胫骨和尺骨。在无负荷组中，维拉帕米和PTH治疗均未显著改变任何骨形成参数。这项研究表明，L型VSCC介导体内负荷诱导的骨形成。此外，PTH通过L型VSCC的参与增强负荷诱导的骨适应。
PTH and mechanical loading might act synergistically on bone formation. We tested the in vivo effect of the L-type voltage-sensitive calcium channel (VSCC) blocker, verapamil, on bone formation induced by human PTH-(1-34) (PTH) injection with or without mechanical loading. Adult rats were divided into eight groups: vehicle, verapamil, PTH, or verapamil plus PTH with or without mechanical loading. Verapamil (100 mg/kg) was given orally 90 min before loading. PTH(80 mug/kg) was injected sc 30 min before loading. Loading applied to tibia and ulna for 3 min significantly increased the bone formation rate on both the endocortical surface of tibia and the periosteal surface of ulna (P < 0.0001). Treatment with PTH enhanced load-induced bone formation by 53% and 76% (P < 0.001) on the endocortical and periosteal surfaces, respectively. Treatment with verapamil suppressed load-induced bone formation rate by 77% and 59% (P < 0.01). Furthermore, verapamil suppressed bone formation in rats subjected to PTH plus loading by 74% and 68% (P< 0.0001) at the tibia and ulna, respectively. In the groups without loading, neither verapamil nor PTH treatment significantly changed any bone formation parameter. This study indicates that L-type VSCCs mediate load-induced bone formation in vivo. Furthermore, PTH enhances load-induced bone adaptation through involvement of L-type VSCCs.