Sclerostin – new target for bone anabolic therapy in low bone mass
More details
Hide details
Online publication date: 2010-07-02
Reumatologia 2010;48(3):183-187
Sclerostin is a potent protein secreted by osteocyte which can inhibit bone formation. A new locus was identified near SOST gene at 17q21 which it encodes. Sclerostin directly binds low density lipoprotein co-receptors Lrp5 and Lrp6 and modulates both bone morphogenetic proteins (BMPs) and Wnt/-catenin signaling pathway. Probably this is the crucial importance for osteogenesis and has probably been the most intensively studied signaling pathway in bone metabolism in recent years. Although much progress has been made in the molecular understanding of bone metabolism in recent years, no therapy is available yet to cure low bone mass and to protect fractures. Many of the current approaches to identify potential therapeutic targets are focused on the Wnt/-catenin signaling pathway.
D'Amelio P, Cristofaro MA, Grimaldi AC, et al. The Role of Circulating Bone Cell Precursors in Fracture Healing. Calcif Tissue Int 2010; 14 Apr 2010 (publikacja on-line). .
Dallas SL, Bonewald LF. Dynamics of the transition from osteoblast to osteocyte. Ann N Y Acad Sci 2010; 1192: 437-443. .
Rochefort GY, Pallu S, Benhamou CL. Osteocyte: the unrecognized side of bone tissue. Osteoporos Int 2010; 4 MAR 2010 (publikacja on-line). .
Chapurlat RD, Delmas PD. Bone microdamage: a clinical perspective. Osteoporos Int 2009; 20: 1299-1308. .
Hamersma H, Gardner J, Beighton P. Natural history of sclerosteosis. Clin Genet 2003; 63: 192-197. .
Truswell AS. Osteopetrosis with syndactyly. A morphological variant of Albers-Schonberg disease. J Bone Joint Surg (Br) 1958; 40: 208-218. .
Hansen HG. Sklerosteose 1967; 351. Opitz H, Schmidt F, et al. Handbuch der Kinderheilkunde. .
Balemans W, Ebeling M, Patel N, et al. Increased bone density in sclerosteosis is due to the deficiency of a novel secreted protein (SOST). Hum Mol Genet 2001; 10: 537-543. .
Balemans W, Patel N, Ebeling M, et al. Identification of a 52 kb deletion downstream of the SOST gene in patients with van Buchem disease. J Med Genet 2002; 39: 91-97. .
Khosala S, Westendor JJ, Oursler MJ. Building bone to reverse osteoporosis and repair fractures. J Clin Invest 2008; 118: 421-428. .
Gaudio A, Pennisi P, Bratengeier C, et al. Increased Sclerostin Serum Levels Associated with Bone Formation and Resorption Markers in Patients with Immobilization-Induced Bone Loss. J Clin Endocrinol Metab 2010 (publikacja on-line). .
Kramer I, Halleux C, Keller H, et al. Osteocyte Wnt/{beta}-catenin signaling is required for normal bone homeostasis Mol Cell Biol 2010 (publikacja on-line). .
Yavropoulou MP, Yovos JG. The role of the Wnt signaling pathway in osteoblast commitment and differentiation. Hormones 2007; 6: 279-294. .
Choi HY, Dieckmann M, Herz J. Lrp4, a novel receptor for Dickkopf 1 and sclerostin, is expressed by osteoblasts and regulates bone growth and turnover in vivo. PLoS One 2009; 4 (11). .
Bodine PVN. Wnt signaling control of bone cell apoptosis. Cell Research 2008; 18: 248-225. .
Bodine PV, Seestaller-Wehr L, Kharode YP. Bone anabolic effects of parathyroid hormone are blunted by deletion of the Wnt antagonist secreted frizzled-related protein-1. J Cell Physiol 2007; 210: 352-357. .
Berdiaki A, Datsis GA, Nikitovic D, et al. Parathyroid hormone (PTH) peptides through the regulation of hyaluronam metabolism affect osteosarcoma cell migration. IUBMB Life 2010; 62: 377-386. .
Ott SM. Sclerostin and Wnt Signaling – the pathway to bone strength. J Clin Endocrinol Metabol 2005; 90: 6741-6743. .
Jackson A, Vayssiere B, Garcia T, et al. Gene array analysis of Wnt-regulated genes in C3H10T1/2 cells. Bone 2005; 36: 585-598. .
Rochefort GY, Pallu S, Benhamou CL. Osteocyte: the unrecognized side of bone tissue. Osteoporos Int 2010 (publikacja on line). .
Warmington K, Ominsky M, Bolon B, et al. Sclerostin monoclonal antibody treatment of osteoporotic rats completely reverses one year of ovariectomy-induced systemic bone loss. J Bone Miner Res 2005; 20: S22. .
Ominsky MS, Vlasseros F, Jolette J, et al. Two doses of sclerosti antibody in cynomolgus monkeys increases bone formation, bone mineral density and bone strength. J Bone Miner Res 2010; 25: 948-959.
Copyright: © Narodowy Instytut Geriatrii, Reumatologii i Rehabilitacji w Warszawie. This is an Open Access journal, all articles are distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0) License (https://creativecommons.org/licenses/by-nc-sa/4.0/), allowing third parties to copy and redistribute the material in any medium or format and to remix, transform, and build upon the material, provided the original work is properly cited and states its license.
Journals System - logo
Scroll to top