Cathepsin K Deficiency Suppresses Disuse-Induced Bone Loss.
Cathepsin K Deficiency Suppresses Disuse-Induced Bone Loss.
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组织蛋白酶 K 缺乏会抑制废用引起的骨质流失。
DOI：
10.1002/jcp.25214
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发表时间：
2016
期刊：
影响因子：
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通讯作者：
Ezura Y.
中科院分区：
文献类型：
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作者：
Moriya S;Izu Y;Arayal S;Kawasaki M;Hata K;Pawaputanon Na Mahasarakhahm C;Izumi Y;Saftig P;Kaneko K;Noda M;Ezura Y.
卸载引起骨丢失和废用性骨质疏松症。然而，废用性骨质疏松症的机制仍不完全清楚。在这里，我们研究了组织蛋白酶K（CatK）缺乏对废用性骨质疏松症的影响，通过使用坐骨神经切除术（Nx）模型。手术4周后，将CatK KO和WT小鼠处死并进行分析。对于富含松质骨的区域，与野生型小鼠假手术侧的骨密度（BMD）相比，Nx降低骨密度（BMD）。相反，CatK缺乏抑制了松质骨中Nx诱导的BMD降低。与野生型小鼠假手术侧相应区域的BMD相比，Nx还降低了中段骨干皮质骨的BMD。相反，CatK缺乏抑制了这种Nx诱导的中段皮质骨BMD降低。在WT小鼠中，Nx降低了骨体积（BV/TV）。相比之下，Cat-K缺乏抑制了这种骨体积的减少。有趣的是，与假手术侧相比，CatK缺乏抑制了Nx侧的破骨细胞数量和破骨细胞表面。当培养从CatK-KO小鼠的Nx侧股骨获得的骨髓细胞时，培养物中的钙化区域的水平增加。基因表达的进一步研究表明，Nx抑制了WT小鼠中编码成骨细胞表型相关分子（如Runx 2和碱性磷酸酶）的基因的表达。相反，CatK缺乏抑制这种减少。这些数据表明CatK参与废用性骨量减少。J.细胞。231：1163-1170，2016。© 2015 Wiley Periodicals，Inc.
Unloading induces bone loss and causes disuse osteoporosis. However, the mechanism underlying disuse osteoporosis is still incompletely understood. Here, we examined the effects of cathepsin K (CatK) deficiency on disuse osteoporosis induced by using sciatic neurectomy (Nx) model. After 4 weeks of surgery, CatK KO and WT mice were sacrificed and subjected to analyses. For cancellous bone rich region, Nx reduced the bone mineral density (BMD) compared to the BMD in the sham operated side in wild type mice. In contrast, CatK deficiency suppressed such Nx‐induced reduction of BMD in cancellous bone. Nx also reduced BMD in the mid shaft cortical bone compared to the BMD in the corresponding region on the sham operated side in wild type mice. In contrast, CatK deficiency suppressed such Nx‐induced reduction of BMD in the mid shaft cortical bone. Bone volume (BV/TV) was reduced by Nx in WT mice. In contrast, Cat‐K deficiency suppressed such reduction in bone volume. Interestingly, CatK deficiency suppressed osteoclast number and osteoclast surface in the Nx side compared to sham side. When bone marrow cells obtained from Nx side femur of CatK‐KO mice were cultured, the levels of the calcified area in culture were increased. Further examination of gene expression indicated that Nx suppressed the expression of genes encoding osteoblast‐phenotype‐related molecules such as Runx2 and alkaline phosphatase in WT mice. In contrast, CatK deficiency suppressed such reduction. These data indicate that CatK is involved in the disuse‐induced bone mass reduction. J. Cell. Physiol. 231: 1163–1170, 2016. © 2015 Wiley Periodicals, Inc.