title: Cathepsin K Deficiency Suppresses Disuse-Induced Bone Loss.
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.
authors.affiliation: Department of Molecular Pharmacology, Tokyo Medical and Dental University, Tokyo, Japan.|Department of Orthopaedic Surgery, Juntendo University School of Medicine, Japan.
authors.forename: Shuichi
authors.initials: S
authors.lastname: Moriya
authors.affiliation: Department of Molecular Pharmacology, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Yayoi
authors.initials: Y
authors.lastname: Izu
authors.affiliation: Department of Molecular Pharmacology, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Smriti
authors.initials: S
authors.lastname: Arayal
authors.affiliation: Department of Molecular Pharmacology, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Makiri
authors.initials: M
authors.lastname: Kawasaki
authors.affiliation: Department of Molecular Pharmacology, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Koki
authors.initials: K
authors.lastname: Hata
authors.affiliation: Department of Molecular Pharmacology, Tokyo Medical and Dental University, Tokyo, Japan.|Department of Periodontology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Japan.
authors.forename: Chantida
authors.initials: C
authors.lastname: Pawaputanon Na Mahasarakhahm
authors.affiliation: Department of Periodontology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Izumi
authors.affiliation: Zentrum Biochemie und Molekulare Zellbiologie, Abteilung Biochemie II, Universität Göttingen, Gosslerstrasse, Göttingen, Germany.
authors.forename: Paul
authors.initials: P
authors.lastname: Saftig
authors.affiliation: Department of Orthopaedic Surgery, Juntendo University School of Medicine, Japan.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Kaneko
authors.affiliation: Department of Molecular Pharmacology, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Noda
authors.affiliation: Department of Molecular Pharmacology, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Ezura
mesh_terms: D000469:Alkaline Phosphatase / Q000235:genetics / Q000378:metabolism; D000818:Animals; D015519:Bone Density; D001854:Bone Marrow Cells / Q000378:metabolism; D001862:Bone Resorption / Q000000981:diagnostic imaging / Q000201:enzymology* / Q000209:etiology* / Q000503:physiopathology; D001842:Bone and Bones / Q000000981:diagnostic imaging / Q000201:enzymology / Q000473:pathology; D002113:Calcification, Physiologic / Q000235:genetics; D056657:Cathepsin K / Q000172:deficiency* / Q000378:metabolism; D002478:Cells, Cultured; D021621:Imaging, Three-Dimensional; D008810:Mice, Inbred C57BL; D020966:Muscular Disorders, Atrophic / Q000150:complications* / Q000000981:diagnostic imaging / Q000201:enzymology* / Q000473:pathology; D009929:Organ Size; D010010:Osteoclasts / Q000473:pathology; D010012:Osteogenesis / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D055114:X-Ray Microtomography
chemical_list: D012333:RNA, Messenger; D000469:Alkaline Phosphatase; D056657:Cathepsin K