Hostname: page-component-cd9895bd7-jn8rn Total loading time: 0 Render date: 2024-12-27T08:41:29.708Z Has data issue: false hasContentIssue false

Genistein modulates the effects of parathyroid hormone in human osteoblastic SaOS-2 cells

Published online by Cambridge University Press:  08 March 2007

Wen-Fang Chen
Affiliation:
Central Laboratory of the Institute of Molecular Technology for Drug Discovery and SynthesisDepartment of Applied Biology and Chemical TechnologyThe Hong Kong Polytechnic UniversityHung HomKowloonHong Kong SARChina Department of PhysiologyMedical College of Qingdao UniversityQingdao 266021China
Man-Sau Wong*
Affiliation:
Central Laboratory of the Institute of Molecular Technology for Drug Discovery and SynthesisDepartment of Applied Biology and Chemical TechnologyThe Hong Kong Polytechnic UniversityHung HomKowloonHong Kong SARChina State Key Laboratory of Chinese Medicine and Molecular PharmacologyShenzhenChina
*
*Corresponding author: Dr Man-Sau Wong, fax +852 23649932, email bcmswong@polyu.edu.hk
Rights & Permissions [Opens in a new window]

Abstract

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.

Genistein and parathyroid hormone (PTH) are anabolic agents that stimulate bone formation through their direct actions in osteoblastic cells. In the present study, we aimed to determinewhether genistein modulates the actions of PTH in human osteoblastic SaOS-2 cells in an oestrogen-depleted condition. The present results showed that genistein (10−8 to 10−6 m) induced alkaline phosphatase (ALP) activity and osteoprotegrin (OPG) expression in SaOS-2 cells in a dose-dependent manner. These effects could be completely abolished by co-treatment with oestrogen antagonist ICI 182780 (7α-[9-[(4,4,5,5,5-pentafluoropentyl)sulfonyl]nonyl]-estra-1,3,5(10)-triene-3,17β-diol). Genistein (at 1μm) could stimulate the mRNA expression of receptor activator of NF-κB ligand (RANKL). As OPG and RANKL are known to modulate osteoclastogenesis, the ability of genistein to modulate OPG and RANKL expression in SaOS-2 cells suggested that it might modulate osteoclastogenesis through its direct actions on osteoblastic cells. PTH (at 10nm) stimulated ALP activity, induced RANKL mRNA expression and suppressed OPG mRNA expression in SaOS-2 cells, confirming its bi-directional effects on osteoblastic cells. Pre-treatment of SaOS-2 cells with genistein andoestrogen not only enhanced PTH-induced ALP activity, but also attenuated PTH up regulation ofRANKL mRNA expression and PTH down regulation of OPG mRNA expression. Taken together, the present study provides the first evidence that genistein could modulate the actions of PTH in human osteoblastic SaOS-2 cells in an oestrogen-depleted condition.

Type
Research Article
Copyright
Copyright © The Nutrition Society 2006

References

Alekel, DL, Germain, AS, Peterson, CT, Hanson, KB, Stewart, JW & Toda, TIsoflavone-rich soy protein isolate attenuates bone loss in the lumbar spine of perimenopausal women. Am J Clin Nutr 2000 72, 844852.CrossRefGoogle ScholarPubMed
Anderson, JB, Chen, XW & Garner, SCEffects of genistein on MT3T3-E1, and osteoclast-like cell in relation to expression of estrogen receptors and during cell differentiation. J Nutr 2000 130, 660S667S.Google Scholar
Anderson, JJ, Ambrose, WWGarner, SCBiphasic effects of genistein on bone tissue in the ovariectomized, lactating rat model. Proc Soc Exp Biol Med 1998 217, 345350.CrossRefGoogle Scholar
Anonymous, Assessment of fracture risk and its application to screening for postmenopausal osteoporosis. Report of a WHO Study Group. World Health Organ Tech Rep Ser 1994 843, 1123.Google Scholar
Bradford, MMA rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 1976 72, 248254.CrossRefGoogle ScholarPubMed
Bucay, NSarosi, IDunstan, CRet al.. Osteoprotegerindeficient mice develop early onset osteoporosis and arterial calcification. Genes Dev 1998 12, 12601268.CrossRefGoogle ScholarPubMed
Chen, X & Anderson, JJBEffects of isoflavones on osteoblast proliferation and differentiation. J Nutr 2002 132, 616S Abstr.Google Scholar
Chen, X, Garner, SC, Quarles, LD & Anderson, JJEffects of genistein on expression of bone markers during MC3T3-E1 osteoblastic cell differentiation. J Nutr Biochem 2003 14, 342349.CrossRefGoogle ScholarPubMed
Cusack, S, Jewell, C & Cashman, KDThe effect of estrogen and selected phytoestrogens on cell viability and molecular markers of SaOS-2 osteoblast-like activity. Ann Nutr Metab 2001 45, 228 Abstr.Google Scholar
Deady, JClinical monograph: hormone replacement therapy. Manag Care Pharm 2004 10, 3347.Google ScholarPubMed
Dempster, DW, Cosman, F, Parisien, M,Shen, V & Lindsay, RAnabolic actions of parathyroid hormone on bone. Endocr Rev 1993 14, 690709.Google ScholarPubMed
Denizot, F & Lang, RRapid colorimetric assay for cell growth and survival. Modifications to the tetrazolium dye procedure giving improved sensitivity and reliability. J Immunol Methods 1986 89, 271277.CrossRefGoogle Scholar
Goldwyn, SLazinsky, A & Wei, HPromotion of health by soy isoflavones: efficacy, benefit and safety concerns. Drug Metabol Drug Interact 2000 17, 261289.CrossRefGoogle ScholarPubMed
Greendale, GA, FitzGerald, GHuang, MH, Sternfeld, B, Gold, E, Seeman, T, Sherman, S, Sowers, MDietary soy isoflavones and bone mineral density: results from the study of women’s health across the nation. Am J Epidemiol 2002 155, 746754.CrossRefGoogle ScholarPubMed
Greenfield, EMHorowitz, MC & Lavish, SAStimulation by parathyroid hormone of interleukin-6 and leukemia inhibitory factor expression in osteoblasts in an immediate-early gene response induced by cAMP signal transduction. J Biol Chem 1996 271, 1098410989.CrossRefGoogle Scholar
Huang, YF, Harrison, JR, Lorenzo, JA & Kream, BEParathyroid hormone induces interleukin-6 heterogenous nuclear and messenger RNA expression in murine calvarial organ cultures. Bone 1998 23, 327332.CrossRefGoogle ScholarPubMed
Khosla, S, Atkinson, EJ, Melton, LJ III & Riggs, BLEffects of age and estrogen status on serum parathyroid hormone levels and biochemical markers of bone turnover in women: a populationbased study. J Clin Endocrinol Metab 1997 82, 15221527.Google Scholar
King, RA & Bursill, DBPlasma and urinary kinetics of the isoflavones daidzein and genistein after a single soy meal in humans. Am J Clin Nutr 1998 67, 867872.CrossRefGoogle ScholarPubMed
Kong, YY, Yoshida, H, Sarosi, Iet al.. OPGL is a key regulator of osteoclastogenesis, lymphocyte development and lymph-node organogenesis. Nature 1999 397, 315323.CrossRefGoogle ScholarPubMed
Lacey, DL, Timms, E, Tan, HLet al.. Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation. Cell 1998 165, 176176.Google Scholar
Lauderdale, DS, Jacobsen, SJFurner, SE, Levy, PS, Brody, JA & Goldberg, JHip fracture incidence among elderly Asian-American populations. Am J Epidemiol 1997 146, 502509.CrossRefGoogle ScholarPubMed
Masiukiewicz, US, Mitnick, M, Grey, AB, & Insogna, KLEstrogen modulates parathyroid hormone-induced interleukin-6 production in vivo and in vitro. Endocrinology 2000 141, 25262531.CrossRefGoogle ScholarPubMed
Massion, CG & Frankenfeld, JKAlkaline phosphatase: lability in fresh and frozen human serum and in lyophilized control material. Clin Chem 1972 18, 366373.CrossRefGoogle ScholarPubMed
Mei, JYeung, SS & Kung, AWHigh dietary phytoestrogen intake is associated with higher bone mineral density in postmenopausal but not premenopausal women. J Clin Endocrinol Metab 2001 86, 52175221.CrossRefGoogle Scholar
Morabito, N, Crisafulli, A, Vergara, Cet al. Effects of genistein and hormone-replacement therapy on bone loss in early postmenopausal women: a randomized double-blind placebo-controlled study. J Bone Miner Res 2002 17, 19041912.CrossRefGoogle Scholar
Murray, E, Provvedini, D, Curran, D, Catherwood, B, Sussman, H, Manolagas, SCharacterization of a human osteoblastic osteosarcoma cell line (SAOS-2) with high bone alkaline phosphatase activity. J Bone Miner Res 1987 2, 231238.CrossRefGoogle ScholarPubMed
Nasu, M, Sugimoto, T, Kaji, H & Chihara, K (2000) Estrogen modulates osteoblast proliferation and function regulated by parathyroid hormone in osteoblastic SaOS-2 cells: role of insulin-like growth factor (IGF)-I and IGF-binding protein-5. J Endocrinol 167, 305313.CrossRefGoogle ScholarPubMed
Onyia, JE, Libermann, TA, Bidwell, J, Bidwell, J, Arnold, D, Tu, Y, McClelland, P & Hock, JMParathyroid hormone (1–34)-mediated interleukin-6 induction. J Cell Biochem 1997 67, 265274.3.0.CO;2-E>CrossRefGoogle ScholarPubMed
Potter, SM, Baum, JA, Teng, HStillman, RJ, Shay, NF & Erdman, JW Jr Soy protein and isoflavones: their effects on blood lipids and bone density in postmenopausal women. Am J Clin Nutr 1998 68, Suppl. 61375S1379S.CrossRefGoogle ScholarPubMed
Rao, LG, Wylie, JN, Sutherland, MS & Murray, TM17 Betaestradiol and parathyroid hormone potentiate each other's stimulatory effects on alkaline phosphatase activity in SaOS-2 cells in a differentiation-dependent manner. Endocrinology 1994 134, 614620.CrossRefGoogle Scholar
Ross, PD, Norimatsu, H, Davis, JW, Yano, K, Wasnich, RD, Fujiwara, S, Hosoda, Y & Melton, LJ IIIA comparison of hip fracture incidence among native Japanese. Japanese Americans, and American Caucasians. Am J Epidemiol 1991 133, 801809.CrossRefGoogle ScholarPubMed
Santell, RCKieu, N & Helferich, WGGenistein inhibits growth of estrogen-independent human breast cancer cells in culture but not in athymic mice. J Nutr 2000 130, 16651669.CrossRefGoogle ScholarPubMed
Slootweg, MC, Ederveen, AG, Schot, LP, Schoonen, WG & Kloosterboer, HJOestrogen and progestogen synergistically stimulate human and rat osteoblast proliferation. J Endocrinol 1992 133, R5R8.CrossRefGoogle ScholarPubMed
Valachovicova, T, Slivova, V & Sliva, DCellular and physiological effects of soy flavonoids.. Mini Rev Med Chem 2004 4, 881887.CrossRefGoogle ScholarPubMed
Viereck, V, Grundker, C, Blaschke, S,Siggelkow, H, Emons, G, Hofbauer, LC (2002) Phytoestrogen genistein stimulates the production of osteoprotegerin by human trabecular osteoblasts. Cell Biochem 84 725735.CrossRefGoogle ScholarPubMed
Yamagishi, T, Otsuka, E & Hagiwara, HReciprocal control of expression of mRNAs for osteoclast differentiation factor and OPG in osteogenic stromal cells by genistein: evidence for the involvement of topoisomerase II in osteoclastogenesis. Endocrinology 2001 142, 36323637.CrossRefGoogle ScholarPubMed
Yao, GQ, Sun, B, Hammond, EE, Spencer, EN, Horowitz, MC, Insogna, KL & Weir, ECThe cell-surface form of colony-stimulating factor-1 is regulated by osteotropic agents and supports formation of multinucleated osteoclast-like cells. J Biol Chem 1998 237, 41194129.CrossRefGoogle Scholar
Yasuda, H, Shima, N, Nakagawa, Net al. Osteoclast differentiation factor is a ligand for osteoprotegerin/osteoclastogenesisinhibitory factor and is identical to TRANCE/RANKL. Proc Natl Acad Sci U S A 1998 95, 35973602.CrossRefGoogle ScholarPubMed