The anabolic action of intermittent PTH in combination with cathepsin K inhibitor or alendronate differs depending on the remodeling status in bone in ovariectomized mice.
The anabolic action of intermittent PTH in combination with cathepsin K inhibitor or alendronate differs depending on the remodeling status in bone in ovariectomized mice.
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DOI：
10.1016/j.bone.2008.05.010
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发表时间：
2009-06
期刊：
影响因子：
4.1
通讯作者：
Hirotoshi Yamane;A. Sakai;Toshiharu Mori;Shinya Tanaka;K. Moridera;Toshitaka Nakamura
中科院分区：
文献类型：
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作者：
Hirotoshi Yamane;A. Sakai;Toshiharu Mori;Shinya Tanaka;K. Moridera;Toshitaka Nakamura
我们假设甲状旁腺激素（PTH）与抗分解代谢药物组织蛋白酶K抑制剂和阿仑膦酸钠的合成代谢作用根据骨重建状态而不同。对8周龄的C57/BL/6 J小鼠进行卵巢切除（OVX）或假手术。在手术后6周，用组织蛋白酶K抑制剂、阿仑膦酸盐或媒介物（每天，持续8周）、有或没有PTH（1-34）（5次/周，持续最后4周）治疗小鼠。我们评估了血清和尿液的骨化学标志物、骨密度（BMD）、荧光标记后的胫骨近端初级和次级松质骨的组织形态学、原代细胞培养和骨髓细胞中mRNA的表达。组织蛋白酶K抑制剂和阿仑膦酸钠显着增加骨密度和骨体积的原发性和继发性松质骨，与减少尿I型胶原C-端肽，增加OVX，分别。组织蛋白酶K抑制剂增强了PTH对原发性和继发性松质骨密度和骨体积的合成作用，而阿仑膦酸钠仅对原发性松质骨密度和骨体积有相同的作用。组织蛋白酶K抑制剂不降低血清骨钙素水平，而阿仑膦酸钠可降低血清骨钙素水平，组织蛋白酶K抑制剂不降低破骨细胞数量和骨形成率，而阿仑膦酸钠可降低破骨细胞数量和骨形成率，并增加破骨细胞凋亡。PTH和组织蛋白酶K抑制剂的组合增加碱性磷酸酶阳性CFU-f形成和c-fos，osterix，和骨钙素mRNA表达的骨髓细胞，以及单独的PTH，而PTH和阿仑膦酸钠的组合降低这些值。这项研究表明，阿仑膦酸盐增强PTH在原发性海绵体的合成代谢作用，但在重塑骨小梁中使其钝化，而组织蛋白酶K抑制剂增强OVX小鼠两个部位的作用。总之，间歇性PTH与组织蛋白酶K抑制剂或阿仑膦酸钠组合的合成代谢作用取决于OVX小鼠骨重建状态。
We hypothesized that the anabolic action of parathyroid hormone (PTH) with the anti-catabolic agents cathepsin K inhibitor and alendronate differs depending on the remodeling status in the bone. C57/BL/6J mice, 8 weeks of age, were subjected to ovariectomized (OVX) or sham surgery. At 6 weeks after surgery, the mice were treated with cathepsin K inhibitor, alendronate, or a vehicle (daily, for 8 weeks), with or without PTH (1–34) (5 times/week, for the last 4 weeks). We assessed the bone chemical markers of the serum and urine, bone mineral density (BMD), histomorphomery in the primary and secondary spongiosa of the proximal tibia after fluorescence labeling, primary cell culture, and mRNA expressions in bone marrow cells. Cathepsin K inhibitor and alendronate significantly increased the BMD and the bone volume of the primary and secondary spongiosa, with a reduction of the urinary C-telopeptide of type I collagen that was increased by OVX, respectively. Cathepsin K inhibitor augmented the anabolic action of PTH on the BMD and bone volume at both the primary and secondary spongiosa, while alendronate had the same effect on the BMD and bone volume only at the primary spongiosa. Cathepsin K inhibitor did not decrease serum osteocalcin with or without PTH, while alendronate did decrease it. Cathepsin K inhibitor did not decrease the values of osteoclast number or bone formation rate with or without PTH, while alendronate decreased those values and increased osteoclast apoptosis. The combination of PTH and cathepsin K inhibitor increased alkaline phosphatase-positive CFU-f formation and c-fos, osterix, and osteocalcin mRNA expressions of bone marrow cells as well as PTH alone, while the combination of PTH and alendronate decreased those values. This study demonstrated that alendronate enhances the anabolic action of PTH at the primary spongiosa, but blunts it in the remodeling trabecular bone, while cathepsin K inhibitor enhances the action at both sites in OVX mice. In conclusion, the anabolic action of intermittent PTH in combination with cathepsin K inhibitor or alendronate differs depending on the remodeling status of bone in OVX mice.