Osteoclast markers accumulate on cells developing from human peripheral blood mononuclear precursors

Faust, Judy; Lacey, Dave; Hunt, Pamela S.; Burgess, Teresa L.; Scully, Sheila; Van, Gwyneth; Eli, Alana; Qian, Yi-Xin; Shalhoub, Victoria

doi:10.1002/(sici)1097-4644(19990101)72:1<67::aid-jcb8>3.0.co;2-a

Cited by 94 publications

(61 citation statements)

References 38 publications

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“…CD14 þ osteoclast precursors have been shown to lose and acquire macrophage and osteoclast markers respectively in the process of osteoclast differentiation. 14,16 Our findings indicate that the formation of giant cells in ABC is likely to occur by a similar step-wise process from CD14 þ mononuclear phagocyte precursors.…”

Section: Discussionmentioning

confidence: 58%

CD14− mononuclear stromal cells support (CD14+) monocyte–osteoclast differentiation in aneurysmal bone cyst

Taylor

Kashima

Hemingway

et al. 2012

Laboratory Investigation

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Aneurysmal bone cyst (ABC) is a benign osteolytic bone lesion in which there are blood-filled spaces separated by fibrous septa containing giant cells. The nature of the giant cells in this lesion and the mechanism of bone destruction in ABC is not certain. In this study, we have analysed several characteristics of mononuclear and multinucleated cells in the ABC and examined the cellular and molecular mechanisms of ABC osteolysis. The antigenic and functional phenotype of giant cells in ABC was determined by histochemistry/immunohistochemistry using antibodies to macrophage and osteoclast markers. Giant cells and CD14 þ and CD14À mononuclear cells were isolated from ABC specimens and cultured on dentine slices and coverslips with receptor activator of nuclear factor kB ligand (RANKL) þ /À macrophage-colony stimulating factor (M-CSF) and functional and cytochemical evidence of osteoclast differentiation sought. Giant cells in ABC expressed an osteoclast-like phenotype (CD51 þ , CD14À, cathepsin K þ , TRAP þ ) and were capable of lacunar resorption, which was inhibited by zoledronate, calcitonin and osteoprotegerin (OPG). When cultured with RANKL ± M-CSF, CD14 þ , but not CD14À, mononuclear cells differentiated into TRAP þ multinucleated cells that were capable of lacunar resorption. M-CSF was not necessary for osteoclast formation from CD14 þ cell cultures. CD14À cells variably expressed RANKL, OPG and M-CSF but supported osteoclast differentiation. Our findings show that the giant cells in ABC express an osteoclast-like phenotype and are formed from CD14 þ macrophage precursors. CD14À mononuclear stromal cells express osteoclastogenic factors and most likely interact with CD14 þ cells to form osteoclast-like giant cells by a RANKL-dependent mechanism.Laboratory Investigation (2012) 92, 600-605; doi:10.1038/labinvest.2012.5; published online 13 February 2012 KEYWORDS: aneurysmal bone cyst (ABC); bisophosphonate; bone resorption; giant cell; osteoclast Benign and malignant tumours that contain numerous osteoclast-like giant cells frequently arise in bone and are categorised on the basis of tissue location and histomorphology. 1,2 The mechanism whereby giant cells accumulate and contribute to the osteolysis that accompanies growth of these tumours in bone is not certain. Primary aneurysmal bone cyst (ABC) is a benign cystic giant cell-rich tumour that arises most commonly in the metaphyseal region of a long bone; 1,2 the cysts are filled with blood and the fibrous cyst wall contains fibroblast-like stromal cells, scattered macrophages and osteoclast-like giant cells. The lesion most commonly arises in the first two decades of life and is a clonal proliferation associated with a characteristic rearrangement of the short arm of chromosome 17. [3][4][5] Osteoclasts are formed from marrow-derived circulating precursors, which express a monocyte/macrophage phenotype. 6,7 These mononuclear phagocyte precursors express the receptor activator of nuclear factor kB (RANK) and, in the presence of macrophage-colony stimulating...

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Section: Discussionmentioning

confidence: 58%

CD14− mononuclear stromal cells support (CD14+) monocyte–osteoclast differentiation in aneurysmal bone cyst

Taylor

Kashima

Hemingway

et al. 2012

Laboratory Investigation

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“…15,16 Briefly, PB human CD34 ϩ -enriched stem cells (5 ϫ 10 5 ), obtained by a single leukapheresis of healthy donors treated with granulocyte colony-stimulating factor (G-CSF) for 3 to 5 days, 15 or human PB MNCs at high density (1.5 ϫ 10 6 ), were incubated in a stromal cell-free system with conditioned medium of activated T cells cocultured with HMCLs or purified MM cells in the presence or absence of rhOPG (100 ng/mL and 1 g/mL) or anti-IL-7 polyclonal antibody (0.03 g/mL) or anti-IgG for 10 days. At the end of the culture period osteoclasts (OCs) were identified as tartrate-resistant acid phosphatase (TRAP ϩ ) multinucleated cells (Sigma-Aldrich, Milan, Italy) according to the manufacturer's instructions.…”

Section: Osteoclastogenesismentioning

confidence: 99%

Human myeloma cells stimulate the receptor activator of nuclear factor-κB ligand (RANKL) in T lymphocytes: a potential role in multiple myeloma bone disease

Giuliani

Colla

Sala

et al. 2002

Blood

244

178

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The biologic mechanisms involved in the pathogenesis of multiple myeloma (MM) bone disease are not completely understood. Recent evidence suggests that T cells may regulate bone resorption through the cross-talk between the critical osteoclastogenetic factor, receptor activator of nuclear factor-B ligand (RANKL), and interferon ␥ (IFN-␥) that strongly suppresses osteoclastogenesis. Using a coculture transwell system we found that human myeloma cell lines (HMCLs) increased the expression and secretion of RANKL in activated T lymphocytes and similarly purified MM cells stimulated RANKL production in autologous T lymphocytes. In addition, either anti-interleukin 6 (anti-IL-6) or anti-IL-7 antibody inhibited HMCL-induced RANKL overexpression. Consistently, we demonstrated that HMCLs and fresh MM cells express IL-7 mRNA and secrete IL-7 in the presence of IL-6 and that bone marrow (BM) IL-7 levels were significantly higher in patients with MM. Moreover, we found that the release of IFN-␥ by T lymphocytes was reduced in presence of both HMCLs and purified MM cells. Furthermore, in a stromal cell-free system, osteoclastogenesis was stimulated by conditioned medium of T cells cocultured with HMCLs and inhibited by recombinant human osteoprotegerin (OPG; 100 ng/mL to 1 g/mL).

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“…Early studies had demonstrated that OCPs originate from the haematopoietic stem cells (Sheven et al, 1986;Hagenaars et al, 1989;Hattersley & Chambers, 1989;Kurihara et al, 1989;Matayoshi et al, 1996) and circulate in PB (Walker, 1973(Walker, , 1975Kahn & Simmons, 1975;Coccia et al, 1980;Faust et al, 1999;. However, whether OCPs possess surface characteristics that distinguish them from other PBMCs (in particular monocytes) is not known.…”

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confidence: 99%

Characterization of osteoclast precursors in human blood

Shalhoub¹,

Elliott

Chiu

et al. 2000

Br J Haematol

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Osteoclast precursors (OCPs) circulate in the mononuclear fraction of peripheral blood (PB), but their abundance and surface characteristics are unknown. Previous studies suggest that the receptor activator for NF‐κB (RANK) on cytokine‐treated OCPs in mouse bone marrow interacts with osteoprotegerin ligand (OPGL/TRANCE/RANKL/ODF) to initiate osteoclast differentiation. Hence, we used a fluorescent form of human OPGL (Hu‐OPGL‐F) to identify possible RANK‐expressing OCPs in untreated peripheral blood mononuclear cells (PBMCs) using fluorescence‐activated cell sorting analysis. Monocytes [CD14‐phycoerythrin (PE) antibody (Ab) positive (+) cells, 10–15% of PBMCs] all (98–100%) co‐labelled with Hu‐OPGL‐F (n > 18). T lymphocytes (CD3‐PE Ab+ cells, 66% of PBMCs) did not bind Hu‐OPGL‐F; however, B cells (CD19‐PE Ab+ cells, 9% of PBMCs) were also positive for Hu‐OPGL‐F. All Hu‐OPGL‐F+ monocytes also co‐labelled with CD33, CD61, CD11b, CD38, CD45 and CD54 Abs, but not CD34 or CD56 Abs. Hu‐OPGL‐F binding was dose dependent and competed with excess Hu‐OPGL. When Hu‐OPGL‐F+, CD14‐PE Ab+, CD33‐PE Ab+, Hu‐OPGL‐F+/CD14‐PE Ab+ or Hu‐OPGL‐F+/CD33‐PE Ab+ cells were cultured with OPGL (20 ng/ml) and colony‐stimulating factor (CSF)‐1 (25 ng/ml), OC‐like cells readily developed. Thus, all freshly isolated monocytes demonstrate displaceable Hu‐OPGL‐F binding, suggesting the presence of RANK on OCPs in PB; also, OCPs within a purified PB monocyte population form osteoclast‐like cells in the complete absence of other cell types in OPGL and CSF‐1 containing medium.

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Osteoclast markers accumulate on cells developing from human peripheral blood mononuclear precursors

Cited by 94 publications

References 38 publications

CD14− mononuclear stromal cells support (CD14+) monocyte–osteoclast differentiation in aneurysmal bone cyst

CD14− mononuclear stromal cells support (CD14+) monocyte–osteoclast differentiation in aneurysmal bone cyst

Human myeloma cells stimulate the receptor activator of nuclear factor-κB ligand (RANKL) in T lymphocytes: a potential role in multiple myeloma bone disease

Characterization of osteoclast precursors in human blood

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