Osteoclasts from Human Giant Cell Tumors of Bone Lack Estrogen Receptors¹

Abstract

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-alpha and ER-beta 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-alpha and calcitonin receptor (CTR) mRNA and apparently lower levels of ER-beta mRNA. Passaged cultures of tumor mononuclear stromal cells also expressed ER-alpha and low ER-beta but not CTR mRNA. In pure preparations of microisolated osteoclasts, expression of ER-alpha or ER-beta mRNA was not detected, whereas expression of CTR mRNA was readily identified. Microisolated GCT mononuclear cells expressed ER-alpha, but no detectable CTR mRNA. Fluorescence in situ hybridization (FISH) using an ER-alpha 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. 17Beta-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.

Diagnosing giant cell tumor of the bone using positron emission tomography/computed tomography: A retrospective study of 20 patients from a single center

“…These giant cells share the same specific markers as osteoclasts, including tartrate-resistant acid phosphatase (21), cathepsin K (22), carbonic anhydrase II (23), calcitonin receptor (24) and receptor activator of nuclear factor κ-light-chain-enhancer of activated B cells (25), and are similarly capable of bone resorption. Giant cells are, however, substantially larger than the osteoclasts and contain hundreds of nuclei (26).…”

Cross-Species and Interassay Comparisons of Phytoestrogen Action

“…The role of estrogen receptors in these actions is unclear. Although both ERα and ERβ are expressed in human (146) and rat (147) osteoblasts, there is no convincing evidence for either in osteoclasts (148), and preosteoclastic cells have not been examined. Unlike other isoflavonoids, IPR does not displace E 2 binding in MCF7 cells or induce ERα-dependent gene transcription (149).…”

Bioactive glass air‐abrasion promotes healing around contaminated implant surfaces surrounded by circumferential bone defects: An experimental study in the rat

“…This is probably related to the Zn 2+ ion release from the Zn‐containing BAG, as demonstrated in our previous study 31 . Zn 2+ ion is an essential element for the growth, proliferation, and differentiation of osteoblast cells, but it can also stimulate osteoblast cell attachment and inhibit osteoclastic cell activity 36,37 . Moreover, silicate ion release from 45S5 BAG has been shown to play an essential role in stimulating the proliferation and differentiation of osteoblast cells 38,39 …”

“…31 Zn 2+ ion is an essential element for the growth, proliferation, and differentiation of osteoblast cells, but it can also stimulate osteoblast cell attachment and inhibit osteoclastic cell activity. 36,37 Moreover, silicate ion release from 45S5 BAG has been shown to play an essential role in stimulating the proliferation and differentiation of osteoblast cells. 38,39 Implant surface decontamination is a crucial step in treating periimplant disease.…”