1. Cathepsin K Deficiency Suppresses Disuse-Induced Bone Loss.
- Author
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Moriya S, Izu Y, Arayal S, Kawasaki M, Hata K, Pawaputanon Na Mahasarakhahm C, Izumi Y, Saftig P, Kaneko K, Noda M, and Ezura Y
- Subjects
- Alkaline Phosphatase genetics, Alkaline Phosphatase metabolism, Animals, Bone Density, Bone Marrow Cells metabolism, Bone Resorption diagnostic imaging, Bone Resorption physiopathology, Bone and Bones diagnostic imaging, Bone and Bones enzymology, Bone and Bones pathology, Calcification, Physiologic genetics, Cathepsin K metabolism, Cells, Cultured, Imaging, Three-Dimensional, Mice, Inbred C57BL, Muscular Disorders, Atrophic diagnostic imaging, Muscular Disorders, Atrophic pathology, Organ Size, Osteoclasts pathology, Osteogenesis genetics, RNA, Messenger genetics, RNA, Messenger metabolism, Real-Time Polymerase Chain Reaction, X-Ray Microtomography, Bone Resorption enzymology, Bone Resorption etiology, Cathepsin K deficiency, Muscular Disorders, Atrophic complications, Muscular Disorders, Atrophic enzymology
- Abstract
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., (© 2015 Wiley Periodicals, Inc.)
- Published
- 2016
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