The Osteocyte As a Therapeutic Target in the Treatment of Osteoporosis

Overview

Journal Ther Adv Musculoskelet Dis

Date 2014 Jun 4

PMID 24891879

Citations 23

Authors

Gael Y Rochefort

Affiliations

Soon will be listed here.

Abstract

Osteoporosis is characterized by a low bone-mineral density associated with skeletal fractures. The decrease in bone-mineral density is the consequence of an unbalanced bone-remodeling process, with higher bone resorption than bone formation. The orchestration of the bone-remodeling process is under the control of the most abundant cell in bone, the osteocyte. Functioning as an endocrine cell, osteocytes are also a source of soluble factors that not only target cells on the bone surface, but also target distant organs. Therefore, any drugs targeting the osteocyte functions and signaling pathways will have a major impact on the bone-remodeling process. This review discusses potential advances in drug therapy for osteoporosis, including novel osteocyte-related antiresorptive and anabolic agents that may become available in the coming years.

Citing Articles

LRP4 and Agrin Are Modulated by Cartilage Degeneration and Involved in β-Catenin Signaling in Human Articular Chondrocytes.

Naniwa S, Nishida K, Yoshida A, Nasu Y, Nakahara R, Ohtsuki T Int J Mol Sci. 2025; 26(3).

PMID: 39940775 PMC: 11817251. DOI: 10.3390/ijms26031007.

Water Extract of Nakai Inhibits Osteoclast Differentiation and Alleviates Ovariectomy-Induced Bone Loss.

Gu D, Yang H, Kim S, Lee S, Ha H Int J Mol Sci. 2024; 25(21).

PMID: 39519166 PMC: 11547052. DOI: 10.3390/ijms252111616.

Editorial: Model organisms and experimental models: opportunities and challenges in musculoskeletal physiology.

Renaud M, Joeng K, Rochefort G Front Physiol. 2023; 14:1346490.

PMID: 38148900 PMC: 10749919. DOI: 10.3389/fphys.2023.1346490.

Review on the protective activity of osthole against the pathogenesis of osteoporosis.

Chen J, Liao X, Gan J Front Pharmacol. 2023; 14:1236893.

PMID: 37680712 PMC: 10481961. DOI: 10.3389/fphar.2023.1236893.

Signaling pathways associated with bone loss in inflammatory bowel disease.

Palatianou M, Karamanolis G, Tsentidis C, Gourgiotis D, Papaconstantinou I, Vezakis A Ann Gastroenterol. 2023; 36(2):132-140.

PMID: 36864939 PMC: 9932862. DOI: 10.20524/aog.2023.0785.

References

Sinder B, Eddy M, Ominsky M, Caird M, Marini J, Kozloff K . Sclerostin antibody improves skeletal parameters in a Brtl/+ mouse model of osteogenesis imperfecta. J Bone Miner Res. 2012; 28(1):73-80. PMC: 3524379. DOI: 10.1002/jbmr.1717. View

Lee D, Kim H, Ku S, Kim S, Choi Y, Kim J . Association between polymorphisms in Wnt signaling pathway genes and bone mineral density in postmenopausal Korean women. Menopause. 2010; 17(5):1064-70. DOI: 10.1097/gme.0b013e3181da4da3. View

Sassi N, Laadhar L, Allouche M, Zandieh-Doulabi B, Hamdoun M, Klein-Nulend J . The roles of canonical and non-canonical Wnt signaling in human de-differentiated articular chondrocytes. Biotech Histochem. 2013; 89(1):53-65. DOI: 10.3109/10520295.2013.819123. View

Bonewald L . The amazing osteocyte. J Bone Miner Res. 2011; 26(2):229-38. PMC: 3179345. DOI: 10.1002/jbmr.320. View

Fraher L, Avram R, Watson P, Hendy G, Henderson J, Chong K . Comparison of the biochemical responses to human parathyroid hormone-(1-31)NH2 and hPTH-(1-34) in healthy humans. J Clin Endocrinol Metab. 1999; 84(8):2739-43. DOI: 10.1210/jcem.84.8.5891. View

Wang Y, Liu Y, Rowe D . Effects of transient PTH on early proliferation, apoptosis, and subsequent differentiation of osteoblast in primary osteoblast cultures. Am J Physiol Endocrinol Metab. 2006; 292(2):E594-603. DOI: 10.1152/ajpendo.00216.2006. View

Lavi-Moshayoff V, Wasserman G, Meir T, Silver J, Naveh-Many T . PTH increases FGF23 gene expression and mediates the high-FGF23 levels of experimental kidney failure: a bone parathyroid feedback loop. Am J Physiol Renal Physiol. 2010; 299(4):F882-9. DOI: 10.1152/ajprenal.00360.2010. View

Staehling-Hampton K, Proll S, Paeper B, Zhao L, Charmley P, Brown A . A 52-kb deletion in the SOST-MEOX1 intergenic region on 17q12-q21 is associated with van Buchem disease in the Dutch population. Am J Med Genet. 2002; 110(2):144-52. DOI: 10.1002/ajmg.10401. View

Killock D . Bone: Osteocyte RANKL in bone homeostasis: a paradigm shift?. Nat Rev Rheumatol. 2011; 7(11):619. DOI: 10.1038/nrrheum.2011.151. View

10.

Verborgt O, Gibson G, Schaffler M . Loss of osteocyte integrity in association with microdamage and bone remodeling after fatigue in vivo. J Bone Miner Res. 2000; 15(1):60-7. DOI: 10.1359/jbmr.2000.15.1.60. View

11.

Rochefort G, Pallu S, Benhamou C . Osteocyte: the unrecognized side of bone tissue. Osteoporos Int. 2010; 21(9):1457-69. DOI: 10.1007/s00198-010-1194-5. View

12.

Ke H, Richards W, Li X, Ominsky M . Sclerostin and Dickkopf-1 as therapeutic targets in bone diseases. Endocr Rev. 2012; 33(5):747-83. DOI: 10.1210/er.2011-1060. View

13.

Rosser J, Bonewald L . Studying osteocyte function using the cell lines MLO-Y4 and MLO-A5. Methods Mol Biol. 2011; 816:67-81. DOI: 10.1007/978-1-61779-415-5_6. View

14.

Rybchyn M, Slater M, Conigrave A, Mason R . An Akt-dependent increase in canonical Wnt signaling and a decrease in sclerostin protein levels are involved in strontium ranelate-induced osteogenic effects in human osteoblasts. J Biol Chem. 2011; 286(27):23771-9. PMC: 3129158. DOI: 10.1074/jbc.M111.251116. View

15.

Boudin E, Fijalkowski I, Piters E, Van Hul W . The role of extracellular modulators of canonical Wnt signaling in bone metabolism and diseases. Semin Arthritis Rheum. 2013; 43(2):220-40. DOI: 10.1016/j.semarthrit.2013.01.004. View

16.

John M, Widler L, Gamse R, Buhl T, Seuwen K, Breitenstein W . ATF936, a novel oral calcilytic, increases bone mineral density in rats and transiently releases parathyroid hormone in humans. Bone. 2011; 49(2):233-41. DOI: 10.1016/j.bone.2011.04.007. View

17.

Khan A, Khan A . Anabolic agents: a new chapter in the management of osteoporosis. J Obstet Gynaecol Can. 2006; 28(2):136-41. DOI: 10.1016/s1701-2163(16)32063-1. View

18.

Liu C, Tu Y, Sun X, Jiang J, Jin X, Bo X . Wnt/beta-Catenin pathway in human glioma: expression pattern and clinical/prognostic correlations. Clin Exp Med. 2010; 11(2):105-12. DOI: 10.1007/s10238-010-0110-9. View

19.

Maclean C, Newberry S, Maglione M, McMahon M, Ranganath V, Suttorp M . Systematic review: comparative effectiveness of treatments to prevent fractures in men and women with low bone density or osteoporosis. Ann Intern Med. 2007; 148(3):197-213. DOI: 10.7326/0003-4819-148-3-200802050-00198. View

20.

Leupin O, Piters E, Halleux C, Hu S, Kramer I, Morvan F . Bone overgrowth-associated mutations in the LRP4 gene impair sclerostin facilitator function. J Biol Chem. 2011; 286(22):19489-500. PMC: 3103328. DOI: 10.1074/jbc.M110.190330. View