Immature dendritic cell transdifferentiation into osteoclasts: a novel pathway sustained by the rheumatoid arthritis microenvironment

Rivollier, Aymeric; Mazzorana, Marlène; Tébib, Jacques; Piperno, M.; Aitsiselmi, Tarik; Rabourdin–Combe, Chantal; Jurdic, Pierre; Servet-Delprat, Christine

doi:10.1182/blood-2004-01-0041

Cited by 284 publications

(274 citation statements)

References 40 publications

(53 reference statements)

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“…Osteoclasts are associated with bone destruction in RA joints (6). Their origin in rheumatoid joints has not yet been identified, but findings of previous studies have indicated that bone marrow-derived CD14-positive cells are responsible for the development of osteoclasts and that both monocytes and dendritic cells can differentiate into functional osteoclasts (7)(8)(9)(10). Osteoclast formation requires cellcell interaction between osteoblasts and osteoclast precursors in bone remodeling.…”

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confidence: 99%

Development of an ex vivo cellular model of rheumatoid arthritis: Critical role of cd14‐positive monocyte/macrophages in the development of pannus tissue

Nozaki¹,

Takahashi²,

Ishii³

et al. 2007

Arthritis & Rheumatism

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Objective. To establish an ex vivo cellular model of pannus, the aberrant overgrowth of human synovial tissue (ST).Methods. Inflammatory cells that infiltrated pannus tissue from patients with rheumatoid arthritis (RA) were collected without enzyme digestion, and designated as ST-derived inflammatory cells. Single-cell suspensions of ST-derived inflammatory cells were cultured in medium alone. Levels of cytokines produced in culture supernatants were measured using enzyme-linked immunosorbent assay kits. ST-derived inflammatory cells were transferred into the joints of immunodeficient mice to explore whether these cells could develop pannus. CD14 and CD2 cells were depleted by negative selection.Results Conclusion. These findings suggest that overgrowth of inflammatory cells from human rheumatoid synovium simulates the development of pannus. This may prove informative in the screening of potential antirheumatic drugs.

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confidence: 99%

Development of an ex vivo cellular model of rheumatoid arthritis: Critical role of cd14‐positive monocyte/macrophages in the development of pannus tissue

Nozaki¹,

Takahashi²,

Ishii³

et al. 2007

Arthritis & Rheumatism

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“…In RA, the DCs are essential for initiation and perpetuation by Ag presentation as well as for cytokine and chemokine secretion (5,6). Furthermore, DCs are capable of transdifferentiating into osteoclasts, contributing directly to bone erosion (7,8). The maturation state of the DCs is crucial for determining the balance between tolerance and immunity.…”

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confidence: 99%

Collagen Induces Maturation of Human Monocyte-Derived Dendritic Cells by Signaling through Osteoclast-Associated Receptor

Schultz

Nitze

Zeuthen

et al. 2015

The Journal of Immunology

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Osteoclast-associated receptor (OSCAR) is widely expressed on human myeloid cells. Collagen types (Col)I, II, and III have been described as OSCAR ligands, and ColII peptides can induce costimulatory signaling in receptor activator for NF-κB–dependent osteoclastogenesis. In this study, we isolated collagen as an OSCAR-interacting protein from the membranes of murine osteoblasts. We have investigated a functional outcome of the OSCAR–collagen interaction in human monocyte-derived dendritic cells (DCs). OSCAR engagement by ColI/II-induced activation/maturation of DCs is characterized by upregulation of cell surface markers and secretion of cytokines. These collagen-matured DCs (Col-DCs) were efficient drivers of allogeneic and autologous naive T cell proliferation. The T cells expanded by Col-DCs secreted cytokines with no clear T cell polarization pattern. Global RNA profiling revealed that multiple proinflammatory mediators, including cytokines and cytokine receptors, components of the stable immune synapse (namely CD40, CD86, CD80, and ICAM-1), as well as components of TNF and TLR signaling, are transcriptional targets of OSCAR in DCs. Our findings indicate the existence of a novel pathway by which extracellular matrix proteins locally drive maturation of DCs during inflammatory conditions, for example, within synovial tissue of rheumatoid arthritis patients, where collagens become exposed during tissue remodeling and are thus accessible for interaction with infiltrating precursors of DCs.

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“…Important bone diseases, such as osteoporosis, rheumatoid arthritis, Paget's disease, and bone metastasis of breast and prostate cancers, are caused by increased osteoclast number and activity (1,2). Osteoclasts, the multinuclear cells, differentiate from hematopoietic precursors of the monocyte/macrophage lineage that also give rise to macrophages or dendritic cells (3,4).…”

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confidence: 99%

IL-3 Inhibits Human Osteoclastogenesis and Bone Resorption through Downregulation of c-Fms and Diverts the Cells to Dendritic Cell Lineage

Gupta

Barhanpurkar

Tomar

et al. 2010

The Journal of Immunology

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IL-3 is an important cytokine that regulates hematopoiesis and functions as a link between the immune and the hematopoietic system. In this study, we investigated the role and mechanism of IL-3 action on human osteoclast formation and bone resorption using PBMCs. PBMCs differentiate into functional osteoclasts in the presence of M-CSF and receptor activator of NF-κB ligand as evaluated by 23c6 expression and bone resorption. We found that IL-3 dose-dependently inhibited formation of 23c6-positive osteoclasts, bone resorption and C-terminal telopeptide of type I collagen, a collagen degradation product. The inhibitory effect of IL-3 on bone resorption was irreversible. To investigate the mechanism of IL-3 action, we analyzed the effect of IL-3 on the receptor activator of NF-κB and c-Fms receptors and c-Fos, PU.1, NFAT cytoplasmic 1, and RelB transcription factors essential for osteoclastogenesis. IL-3 significantly inhibited c-Fms and downregulated both PU.1 and c-Fos at both mRNA and protein level. Furthermore, IL-3–treated cells showed increased expression of dendritic cell markers CD1a and CD80 and decreased expression of monocyte/macrophage marker CD14. Interestingly, IL-3 inhibited formation of human osteoclasts derived from blood monocytes and bone marrow cells of osteoporotic individuals. Thus, IL-3 may have therapeutic potential as an antiosteolytic agent in treatment of osteoporosis.

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Immature dendritic cell transdifferentiation into osteoclasts: a novel pathway sustained by the rheumatoid arthritis microenvironment

Cited by 284 publications

References 40 publications

Development of an ex vivo cellular model of rheumatoid arthritis: Critical role of cd14‐positive monocyte/macrophages in the development of pannus tissue

Development of an ex vivo cellular model of rheumatoid arthritis: Critical role of cd14‐positive monocyte/macrophages in the development of pannus tissue

Collagen Induces Maturation of Human Monocyte-Derived Dendritic Cells by Signaling through Osteoclast-Associated Receptor

IL-3 Inhibits Human Osteoclastogenesis and Bone Resorption through Downregulation of c-Fms and Diverts the Cells to Dendritic Cell Lineage

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