Cathepsin S controls adipocytic and osteoblastic differentiation, bone turnover, and bone microarchitecture

Abstract Cathepsin S is a cysteine protease that controls adipocyte differentiation and has been implicated in vascular and metabolic complications of obesity. Considering the inverse relation of osteoblasts and adipocytes and their mutual precursor cell, we hypothesized that cathepsin S may also af...

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Published in:	Bone (New York, N.Y.) Vol. 64; pp. 281 - 287
Main Authors:	Rauner, M, Föger-Samwald, U, Kurz, M.F, Brünner-Kubath, C, Schamall, D, Kapfenberger, A, Varga, P, Kudlacek, S, Wutzl, A, Höger, H, Zysset, P.K, Shi, G.P, Hofbauer, L.C, Sipos, W, Pietschmann, P
Format:	Journal Article
Language:	English
Published:	Amsterdam Elsevier Inc 01-07-2014 Elsevier
Subjects:	Adipocyte Adipocytes - cytology Animals Biological and medical sciences Bone and Bones - ultrastructure Bone remodeling Bone Remodeling - physiology Cathepsin S Cathepsins - physiology Cell Differentiation - physiology Fundamental and applied biological sciences. Psychology Mice Mice, Knockout Orthopedics Osteoblast Osteoblasts - cytology Osteoclast Real-Time Polymerase Chain Reaction Skeleton and joints Vertebrates: anatomy and physiology, studies on body, several organs or systems Vertebrates: osteoarticular system, musculoskeletal system X-Ray Microtomography Osteoblast Adipocyte Osteoclast Cathepsin S Bone remodeling Peptidases Cathepsin Enzyme Morphology Hydrolases Bone
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Summary:	Abstract Cathepsin S is a cysteine protease that controls adipocyte differentiation and has been implicated in vascular and metabolic complications of obesity. Considering the inverse relation of osteoblasts and adipocytes and their mutual precursor cell, we hypothesized that cathepsin S may also affect osteoblast differentiation and bone remodeling. Thus, the fat and bone phenotypes of young (3 months old) and aged (12 or 18 months old) cathepsin S knock-out (KO) and wild-type (WT) mice were determined. Cathepsin S KO mice had a normal body weight at both ages investigated, even though the amount of subscapular and gonadal fat pads was reduced by 20%. Further, cathepsin S deficiency impaired adipocyte formation (− 38%, p < 0.001), which was accompanied by a lower expression of adipocyte-related genes and a reduction in serum leptin, IL-6 and CCL2 (p < 0.001). Micro-CT analysis revealed an unchanged trabecular bone volume fraction and density, while tissue mineral density was significantly lower in cathepsin S KO mice at both ages. Aged KO mice further had a lower cortical bone mass (− 2.3%, p < 0.05). At the microarchitectural level, cathepsin S KO mice had thinner trabeculae (− 8.3%), but a better connected trabecular network (+ 24%). Serum levels of the bone formation marker type 1 procollagen amino-terminal-propeptide and osteocalcin were both 2–3-fold higher in cathepsin S KO mice as was the mineralized surface. Consistently, osteogenic differentiation was increased 2-fold along with an increased expression of osteoblast-specific genes. Interestingly, serum levels of C-terminal telopeptide of type I collagen were also higher (+ 43%) in cathepsin S KO mice as were histological osteoclast parameters and ex vivo osteoclast differentiation. Thus, cathepsin S deficiency alters the balance between adipocyte and osteoblast differentiation, increases bone turnover, and changes bone microarchitecture. Therefore, bone and fat metabolisms should be monitored when using cathepsin S inhibitors clinically.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	8756-3282 1873-2763
DOI:	10.1016/j.bone.2014.04.022