This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Collier, F. McL. Articles by Nicholson, G. C. Search for Related Content PubMed PubMed Citation Articles by Collier, F. McL. Articles by Nicholson, G. C. Pubmed/NCBI databases Medline Plus Health Information Bone Cancer

Osteoclasts from Human Giant Cell Tumors of Bone Lack Estrogen Receptors¹

The University of Melbourne, Department of Medicine (F.M.C., W.R.H., J.M.H., G.C.N.), The Geelong Hospital, Box 281, Geelong 3220, Australia; Department of Orthopaedic Surgery (W.H.H., L.L.D., M.H.Z.), University of Western Australia, QEII Medical Centre, Nedlands, Western Australia 6009, Australia; St. Vincent’s Institute of Medical Research and The University of Melbourne, Department of Medicine (M.T.G.), Fitzroy 3065, Australia

Address all correspondence and requests for reprints to: Professor G. C. Nicholson, The University of Melbourne, Department of Medicine, The Geelong Hospital, P.O. Box 281, Geelong 3220, Australia. E-mail: G.Nicholson{at}medicine.unimelb.edu.au

Although estrogen is important in human skeletal homeostasis, the major target cell in bone is unknown. Estrogen receptors (ER) have been demonstrated in osteoblasts and bone marrow stromal cells, but their presence in osteoclasts remains controversial because completely pure preparations have not been available. We have examined expression of ER- and ER-ß messenger RNA (mRNA) by RT-PCR in samples from human giant cell tumor of bone (GCT), including: whole tumor, cultured mononuclear cells, and a pure osteoclast population obtained by microisolation. Whole tumor expressed both ER- and calcitonin receptor (CTR) mRNA and apparently lower levels of ER-ß mRNA. Passaged cultures of tumor mononuclear stromal cells also expressed ER- and low ER-ß but not CTR mRNA. In pure preparations of microisolated osteoclasts, expression of ER- or ER-ß mRNA was not detected, whereas expression of CTR mRNA was readily identified. Microisolated GCT mononuclear cells expressed ER-, but no detectable CTR mRNA. Fluorescence in situ hybridization (FISH) using an ER- riboprobe demonstrated strong signal in the mononuclear cells but multinucleated osteoclasts showed no detectable signal. In contrast, CTR mRNA was detected in multinucleated osteoclasts but not in stromal-like tumor cells by FISH. 17ß-estradiol consistently showed no effect on bone resorbing activity of osteoclasts from GCT cultured on cortical bone, although calcitonin was a potent inhibitor. These findings indicate that significant expression of ER does not occur in osteoclasts derived from human GCT and suggest that estrogen effects are mediated by other cells of the bone environment.

This article has been cited by other articles:

				V. Parikka, Z. Peng, T. Hentunen, J. Risteli, T. Elo, H K. Vaananen, and P. Harkonen Estrogen responsiveness of bone formation in vitro and altered bone phenotype in aged estrogen receptor-{alpha}-deficient male and female mice Eur. J. Endocrinol., February 1, 2005; 152(2): 301 - 314. [Abstract] [Full Text] [PDF]

				D. Vanderschueren, L. Vandenput, S. Boonen, M. K. Lindberg, R. Bouillon, and C. Ohlsson Androgens and Bone Endocr. Rev., June 1, 2004; 25(3): 389 - 425. [Abstract] [Full Text] [PDF]

				H Sakai, S Jingushi, T Shuto, K Urabe, T Ikenoue, K Okazaki, T Kukita, A Kukita, and Y Iwamoto Fibroblasts from the inner granulation tissue of the pseudocapsule in hips at revision arthroplasty induce osteoclast differentiation, as do stromal cells Ann Rheum Dis, February 1, 2002; 61(2): 103 - 109. [Abstract] [Full Text] [PDF]

				L. Huang, J. Xu, D. J. Wood, and M. H. Zheng Gene Expression of Osteoprotegerin Ligand, Osteoprotegerin, and Receptor Activator of NF-{kappa}B in Giant Cell Tumor of Bone : Possible Involvement in Tumor Cell-Induced Osteoclast-Like Cell Formation Am. J. Pathol., March 1, 2000; 156(3): 761 - 767. [Abstract] [Full Text] [PDF]

				Estrogen: Consequences and Implications of Human Mutations in Synthesis and Action J. Clin. Endocrinol. Metab., December 1, 1999; 84(12): 4677 - 4694. [Abstract] [Full Text]

				T. C. Spelsberg, M. Subramaniam, B. L. Riggs, and S. Khosla The Actions and Interactions of Sex Steroids and Growth Factors/Cytokines on the Skeleton Mol. Endocrinol., June 1, 1999; 13(6): 819 - 828. [Full Text]