Calcitonin alters behaviour of isolated osteoclasts

Chambers, T.J.; Magnus, Christopher

doi:10.1002/path.1711360104

Cited by 495 publications

(219 citation statements)

References 10 publications

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“…The cells were then incubated for 5min, 10min, 30 min, 1 h and 2 h before formalin fixation for staining (Giemsa). The effectiveness of the CT used in this experiment to inhibit osteoclast motility and induce the characteristic change in osteoclast morphology was confirmed by adding the same CT solution to neonatal rodent osteoclasts which had been isolated in a similar manner as previously described (Chambers & Magnus, 1982).…”

Section: Preparation Of Isolated Giant Cellsmentioning

confidence: 56%

“…However, bone resorption by OMGCs significantly differs from that of isolated osteoclasts in that it is directly stimulated by PTH and not inhibited by calcitonin McSheehy & Chambers, 1986a,b). PTH stimulation of osteoclastic bone resorption has only previously been seen when osteoclasts are incubated in the presence of osteoblasts, and osteoclastic bone resorption is also directly inhibited by calcitonin, a feature which is reflected by the characteristic change in the shape of the cell (Chambers & Magnus, 1982). This morphological response to calcitonin was not exhibited by OMGCs isolated in shortterm cultures on coverslips.…”

Section: Discussionmentioning

confidence: 89%

See 1 more Smart Citation

The origin and nature of stromal osteoclast-like multinucleated giant cells in breast carcinoma: implications for tumour osteolysis and macrophage biology

Athanasou

Wells²,

Quinn³

et al. 1989

Br J Cancer

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(Fry, 1927;Agnantis & Rosen, 1978;Factor et al., 1977;Holland & van Haelst, 1984;Nielsen & Kiaer, 1985;Tavassoli & Norris, 1986) and tumours in other extraskeletal sites (Andreev et al., 1964;Dorney, 1967;Nishiyama et al., 1972; EshunWilson, 1973;Balogh et al., 1985; Berendt et al., 1985). The origin and nature of these cells and their relationship to osteoclasts and macrophage polykaryons is unknown. They are present in the tumour stroma and are generally thought to represent part of the host reponse to the tumour rather than a type of tumour cell. However, their precise function and pathological significance is yet to be determined.In this study, we have examined the ultrastructure and antigenic phenotype of osteoclast-like stromal multinucleate giant cells (OMGCs) in a case of breast carcinoma. We have employed a wide range of monoclonal antibodies of defined specificity in order to clarify the relationship between OMGCs, tumour cells, the osteoclast and other cells of the mononuclear phagocyte system. In addition, we have functionally assessed whether OMGCs behaved like osteoclasts by observing their response to calcitonin and their ability to resorb bone in the presence and absence of known hormonal factors influencing bone resorption. Our findings have implications for macrophage biology and tumour associated osteolysis. Materials and methodsBovine parathyroid hormone (PTH) (2,500 U mg-1) was provided by Dr J. Zanelli (National Institute for Biological Standards, London, UK) and dissolved (230 IU ml-1) in 1 ml 0.001 % acetic acid in distilled water containing 1 mg ml-I of bovine serum albumin (Sigma, UK) (BSA (Welwyn Garden City, UK) and dissolved in alcohol. Tissue culture medium used throughout was Eagles Minimal Essential Medium (Flow, UK), supplemented with benzyl penicillin 100 IU ml-1 (Glaxo, UK) and streptomycin 100 pg ml-1 (Glaxo) (MEM); this was used alone for cell isolation and supplemented with 10% heat inactivated FCS (Gibco, UK) (MEM/FCS) for subsequent incubations.Blocks of cortical bone were obtained at necropsy from the femoral midshaft of patients who had died without evidence of bone disease. These were cleaned of adherent soft tissues then cut longitudinally into bone slices (5 x 3 x 0.3 mm approx) with a low-speed bone saw using a diamond wheel (Buehler Isomet, IL). The bone slices were ultrasonicated for 15min in sterile distilled water, washed in acetone and ethanol then stored dry at room temperature.Anorganic bone slices were prepared by placing bone slices in 5 ml of hot (55°C) 1,2 ethanediamine (Hydrazine) (Eastman, UK). The solution was changed after one hour and the bone slices then kept in hot hydrazine overnight (Termine et al., 1973). The bone slices were washed several times in alcohol then left overnight in alcohol. They were then washed in distilled water, dried and transferred to a sterile petri dish and kept at room temperature until used.Patient details A 45-year-old woman had noted a lump in the upper outer quadrant of her left breast which had recently increased in s...

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Section: Preparation Of Isolated Giant Cellsmentioning

confidence: 56%

Section: Discussionmentioning

confidence: 89%

The origin and nature of stromal osteoclast-like multinucleated giant cells in breast carcinoma: implications for tumour osteolysis and macrophage biology

Athanasou

Wells²,

Quinn³

et al. 1989

Br J Cancer

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“…The most characteristic features of osteoclasts are the presence of ruffled borders and sealing zones. The sealing zones serve to attach osteoclasts to the bone surface and isolate the resorption areas from the surrounding areas (Chambers and Magnus 1982;Väänänen et al 2000). It has been reported that disruption of the sealing zones suppresses the boneresorbing activities of osteoclasts (Lakkakorpi and Väänänen 2004;Nakamura et al 1991;Suzuki et al 1996).…”

Section: Discussionmentioning

confidence: 99%

Inhibitory effect of luteolin on osteoclast differentiation and function

et al. 2009

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Osteoclasts are multinucleated cells that play a crucial role in bone resorption, and are formed by the fusion of mononuclear osteoclasts derived from osteoclast precursors of the macrophage lineage. Compounds that specifically target functional osteoclasts would be ideal candidates for anti-resorptive agents for clinical applications. In the present study, we investigated the effects of luteolin, a flavonoid, on the regulation of receptor activator of nuclear factorjB ligand (RANKL)-induced osteoclastogenesis, functions and signaling pathway. Addition of luteolin to a coculture system of mouse bone marrow cells and ST2 cells in the presence of 10 -8 M 1a,25(OH) 2 D 3 caused significant inhibition of osteoclastogenesis. Luteolin had no effects on the 1a,25(OH) 2 D 3 -induced expressions of RANKL, osteoprotegerin and macrophage colony-stimulating factor mRNAs. Next, we examined the direct effects of luteolin on osteoclast precursors using bone marrow macrophages and RAW264.7 cells. Luteolin completely inhibited RANKL-induced osteoclast formation. Moreover, luteolin inhibited the bone resorption by mature osteoclasts accompanied by the disruption of their actin rings, and these effects were reversely induced by the disruption of the actin rings in mature osteoclasts. Finally, we found that luteolin inhibited RANKLinduced osteoclastogenesis through the suppression of ATF2, downstream of p38 MAPK and nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 1 (NFATc1) expression, respectively. Taken together, the present results indicate that naturally occurring luteolin has inhibitory activities toward both osteoclast differentiation and functions through inhibition of RANKL-induced signaling pathway as well as actin ring disruption, respectively.

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“…Unlike osteoclasts, they were TRAP negative, CD14 positive (Athanasou & Quinn, 1990) and did not respond morphologically to calcitonin (Chambers & Magnus, 1982). No multinucleated cells were present amongst the isolated cells.…”

Section: Resultsmentioning

confidence: 92%

“…Cells cultured on glass coverslips for similar periods were assessed for several osteoclast characteristics viz. morphological response to salmon calcitonin (Rorer Pharmaceuticals, UK) 1 tg ml-' (Chambers & Magnus, 1982), acid phosphatase (AP) and tartrate-resistant acid phosphatase (TRAP) staining (Minkin, 1982) as well as indirect immunoperoxidase staining for CD14 (UCHMI) and CD68 (EBM/1 1) (Athanasou & Quinn, 1990) (macrophage-associated antigens) and epithelial cytokeratin (LP34) (Dakopatts a/s).…”

Section: Methodsmentioning

confidence: 99%

Human tumour-associated macrophages are capable of bone resorption

Athanasou

Quinn²

1992

Br J Cancer

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Summary Cellular mechanisms of bone resorption associated with skeletal metastasis are poorly understood. Human tumour-associated macrophages (TAMs) isolated from primary lung carcinomas were incubated on bone slices where they formed resorption lacunae after 14 days co-culture with a mouse marrow-derived stromal cell line (ST2) with added la, 25-dihydroxy Vitamin D3 and dexamethasone. These co-cultures were associated with the formation of increased numbers of tartrate resistant acid phosphatase positive mononuclear and multinucleated cells. (Galasko, 1976), but the contribution of other cells, principally tumour cells and tumour-associated macrophages (TAMs) within the tumour deposits in bone, is uncertain (Galasko, 1976;Galasko, 1982;Eilon & Mundy, 1978; Koeffier et al., 1978;Novak et al., 1984). This is largely because direct evidence of bone resorption by these cells has not clearly been demonstrated. However, there is now increasing evidence to show that mononuclear phagocytes derived from inflammatory and neoplastic lesions are capable of bone resorption (Athanasou et al., 1989;Athanasou et al., 1991;Athanasou et al., 1992), and that osteoclast-like cells can form directly from tissue macrophages (Udagawa et al., 1990). Materials and methodsTAMs were isolated from five pneumoonectomy specimens for lung carcinoma (three adenocarcinomas; two squamous carcinomas) by collagenase digestion and substrate adherence from 2 x 2 x 2 cm portion of tumour (McGee & Myrvik, 1981), and alveolar macrophages (AMs) from equal portions of lung uninvolved by tumour (Haskill, 1981). TAM or AM-containing cell suspensions in alpha minimal essential medium plus 10% foetal calf serum (Gibco) (MEM/FCS) were added to 6mm wells (500cells/well) containing either bone slices or glass coverslips, half of which had been seeded (1,000 cells/well) 24 h earlier with the mouse marrow stromal cell line ST2 (Riken cell bank, Japan) (Athanasou et al., 1989). Four bone slices (half previously seeded with ST2 cells) were studied for each variable, and cell cultures were incubated at 37°C (5% CO2). After settling for 1 h, these were washed vigorously in MEM/FCS and placed in 16 mm wells containing aMEM/FCS. Dexamethasone (Sigma, UK) (10-7 M) and 1,25 dihydroxy Vitamin D3 (Roche, UK) (10-8 M) were added at the beginning of co-cultures with ST2 cells and at each change of medium (every 3 days). Adherent cells on bone slices were cultured for 24 h, 3, 7 and 14 days after which evidence of bone resorption was sought by scanning electron microscopy (SEM) (Chambers et al., 1984). The effect of PTH (NIBSC, UK) (10 IU ml), PGE2 (Sigma, UK) (10-5 M) and conditioned medium (derived from culture of ST2 cells alone) on bone resorption by TAMs and AMs isolated from two of the above specimens was also examined. Cells cultured on glass coverslips for similar periods were assessed for several osteoclast characteristics viz. morphological response to salmon calcitonin (Rorer Pharmaceuticals, UK) 1 tg ml-' (Chambers & Magnus, 1982), acid phosphatase (AP) and tart...

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Calcitonin alters behaviour of isolated osteoclasts

Cited by 495 publications

References 10 publications

The origin and nature of stromal osteoclast-like multinucleated giant cells in breast carcinoma: implications for tumour osteolysis and macrophage biology

The origin and nature of stromal osteoclast-like multinucleated giant cells in breast carcinoma: implications for tumour osteolysis and macrophage biology

Inhibitory effect of luteolin on osteoclast differentiation and function

Human tumour-associated macrophages are capable of bone resorption

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