Inhibition of cathepsin K promotes osseointegration of titanium implants in ovariectomised rats.
Inhibition of cathepsin K promotes osseointegration of titanium implants in ovariectomised rats.
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DOI：
10.1038/srep44682
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发表时间：
2017-03-17
影响因子：
4.6
通讯作者：
Zhang Y
中科院分区：
文献类型：
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作者：
Yi C;Hao KY;Ma T;Lin Y;Ge XY;Zhang Y
骨质疏松症的骨矿物质缺乏对骨内种植体的长期效果构成威胁。组织蛋白酶K抑制剂（CatK）对骨质疏松症患者的骨转换、骨密度和骨强度有显著影响。因此，我们假设在骨质疏松条件下，应用CatK抑制剂（CatKI）可以增加骨内种植体的骨整合。选择高选择性CatKI Odanacatib（ODN）作为实验药物。将16只大鼠随机分为4组：假手术组、卵巢切除术（OVX）+溶媒组、OVX+低剂量ODN（5 mg/kg）组和OVX+高剂量ODN（30 mg/kg）组。将钛植入物置于每只OVX大鼠双侧股骨的远端干骺端。灌胃8周后，CatKI处理增加了移除扭矩、BMD和骨-种植体接触（BIC）。此外，高剂量CatKI比低剂量CatKI发挥更好的影响。此外，CatKI处理不仅强烈抑制CatK基因（CTSK）表达，而且还适度降低成骨细胞相关基因Runx 2、胶原蛋白-1、BSP、Osterix、OPN、SPP 1和ALP的表达。因此，CatKI可以影响成骨细胞相关基因，尽管骨转换的平衡主要是通过CatK抑制实现的。总之，CatKI可防止骨丢失，并在骨质疏松症条件下辅助骨内植入。
The bone mineral deficiency in osteoporosis poses a threat to the long-term outcomes of endosseous implants. The inhibitors of cathepsin K (CatK) significantly affect bone turnover, bone mineral density (BMD) and bone strength in the patients with osteoporosis. Therefore, we hypothesised that the application of a CatK inhibitor (CatKI) could increase the osseointegration of endosseous implants under osteoporotic conditions. Odanacatib (ODN), a highly selective CatKI, was chosen as the experimental drug. Sixteen rats were randomised into 4 groups: sham, ovariectomy (OVX) with vehicle, OVX with low-dose ODN (5 mg/kg) and OVX with high-dose ODN (30 mg/kg). Titanium implants were placed into the distal metaphysis of bilateral femurs of each OVX rat. After 8 weeks of gavaging, CatKI treatment increased the removal torque, BMD and bone-to-implant contact (BIC). Moreover, high-dose CatKI exerted a better influence than low-dose CatKI. Furthermore, CatKI treatment not only robustly suppressed CatK gene (CTSK) expression, but also moderately reduced expression of the osteoblast-related genes Runx2, Collagen-1, BSP, Osterix, OPN, SPP1 and ALP. Thus, CatKI could affect the osteoblast-related genes, although the balance of bone turnover was achieved mainly by CatK inhibition. In conclusion, CatKI prevented bone loss and aided endosseous implantation in osteoporotic conditions.