Tumor necrosis factor-α cooperates with receptor activator of nuclear factor κB ligand in generation of osteoclasts in stromal cell-depleted rat bone marrow cell culture

Komine, Mitsunori; Kukita, Akiko; Kukita, Toshio; Ogata, Yoshiyasu; Hotokebuchi, Takao; Kohashi, Osamu

doi:10.1016/s8756-3282(01)00420-3

Cited by 117 publications

(84 citation statements)

References 54 publications

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“…The molecular mass of RANK, which is around 110 kDa, strongly suggests that Kat1-Ag is a unique cell-surface antigen completely distinct from RANK. Recently, lines of evidence showed that TNF-induces osteoclastogenesis in a mechanism independent from the RANKL/ ODF-RANK system (Azuma et al 2000, Kobayashi et al 2000, Komine et al 2001. The current study also showed a possible mechanism of osteoclastogenesis independent from the RANKL/ODF-RANK system.…”

Section: Figuresupporting

confidence: 73%

Osteoclast differentiation antigen, distinct from receptor activator of nuclear factor kappa B, is involved in osteoclastogenesis under calcitonin-regulated conditions

Kukita

Watanabe

et al. 2001

Journal of Endocrinology

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Although calcitonin has been clinically utilized as a primary treatment for several metabolic bone diseases, its inhibitory effects against osteoclastic function diminish after several days owing to the calcitonin 'escape phenomenon'. We have previously found a unique cell-surface antigen (Kat1-antigen) expressed on rat osteoclasts. Here we show evidence that, in the presence of calcitonin, the Kat1-antigen is involved in osteoclastogenesis. Treatment of bone marrow cultures for forming osteoclast-like cells with anti-Kat1-antigen monoclonal antibody (mAb Kat1) provoked a marked stimulation of osteoclast-like cell formation only in the presence of calcitonin but not in its absence. Osteoclastogenesis stimulated by the receptor activator of nuclear factor kappa B (NF-B) ligand/ osteoclast differentiation factor was further augmented by mAb Kat1 in the presence of calcitonin. Furthermore, even in the presence of the osteoprotegerin/osteoclast inhibitory factor, mAb Kat1 induced osteoclast-like cell formation. Our current data suggest that the Kat1-antigen is a molecule that is distinct from receptor activator of NF-B. The presence of the unique Kat1-antigen on cells in the osteoclast lineage appears to contribute to the fine regulation of osteoclastogenesis in vivo. Expression of this cell-surface molecule in cells in the osteoclast lineage may partly explain the mechanism responsible for the escape phenomenon.

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Section: Figuresupporting

confidence: 73%

Osteoclast differentiation antigen, distinct from receptor activator of nuclear factor kappa B, is involved in osteoclastogenesis under calcitonin-regulated conditions

Kukita

Watanabe

et al. 2001

Journal of Endocrinology

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“…Osteoprotegerin has been identified as a decoy receptor that competes with RANK for binding to RANKL and thereby suppresses osteoclast formation [14]. The results from studies with mice lacking the respective genes have established the key role of RANKL signalling in osteoclast formation and ultimately how skeletal remodelling and bone mass is regulated [15][16][17].Apart from M-CSF and RANKL, inflammatory cytokines such as TNF-a, IL-1, IL-6 and IL-17 also enhance osteoclast formation [18][19][20][21]. The role of IL-18 in osteoclastogenesis remains controversial.…”

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confidence: 99%

IL‐23 promotes osteoclast formation by up‐regulation of receptor activator of NF‐κB (RANK) expression in myeloid precursor cells

et al. 2008

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Inflammation-mediated bone loss is a major feature of various bone diseases including rheumatoid arthritis, osteoarthritis and advanced periodontitis. Enhanced osteoclast development or activity at the inflammation site results in bone resorption. IL-23 is a heterodimeric cytokine belonging to the IL-6/IL-12 family that has been implicated in the pathogenesis of rheumatoid arthritis and demonstrated to play a role in osteoclastogenesis via stimulation of IL-17 production. In this study we investigated whether IL-23 contributes to the regulation of osteoclast differentiation independent of the IL-17 pathway. We show that IL-23 dose-dependently up-regulates receptor activator of NF-jB expression in primary murine bone marrow macrophages and RAW264.7 cells and thereby promotes commitment of myeloid precursor cells to receptor activator of NF-jB ligand-mediated osteoclastic differentiation. However, IL-23 by itself is insufficient to induce osteoclastogenesis. Increased osteoclastic differentiation of cells was associated with enhanced cathepsin K expression and dentine resorption indicating enhanced formation of functional osteoclasts. IL-17 was not detectable in culture supernatants and when added to cultures, did not promote differentiation of RAW264.7 cells. These results demonstrate that IL-23 can act directly on myeloid precursor cells in addition to indirectly stimulating receptor activator of NF-jB ligand production in osteoblasts and explains its potency in driving osteoclast development in inflammation-mediated bone pathology.Key words: Bone resorption . IL-23 . Inflammation . Osteoclast Supporting Information available online IntroductionBone loss associated with chronic inflammation and infection such as in rheumatoid arthritis or periodontitis is due to an imbalance in bone remodelling that favours resorption. In most instances, low bone mass is the consequence of an increase in osteoclast number or excess osteoclastic activity [1][2][3]. Macrophage colony-stimulation factor-1 (M-CSF) and receptor activator of NF-kB ligand (RANKL) are essential cytokines for osteoclast development [4,5]. M-CSF is produced primarily by stromal fibroblasts, osteoblasts and activated T cells and mediates the survival and proliferation of monocyte/macrophage precursors [6,7]. c-Fms is the sole receptor for M-CSF [8]. c-Fms deficient mice develop an osteoclast/macrophage deficiency and associated osteopetrosis [9], indicating an important role for M-CSF in regulation of bone homeostasis. RANKL is a TNF family cytokine produced by activated T cells, which mediates dendritic cell activation [10,11]. However, this cytokine also plays a central role in bone remodelling. Bone marrow stromal cells and osteoblasts produce RANKL and thereby promote osteoclast formation [12], which ties bone resorption to bone synthesis. Activation of receptor actovator of NF kB (RANKL), the receptor for RANKL, commits myeloid precursors to the osteoclast fate [13]. Osteoprotegerin has been identified as a decoy receptor that competes with RANK for ...

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“…In fact, the direct effect plays a critical role under certain conditions in vivo (14). To explain the direct effect of TNF-␣ on osteoclast precursor cells at the molecular level, it has been reported that TNF-␣ up-regulates or activates molecules in proximal RANK signaling such as RANK, TNF receptorassociated factor 6, and NF-B (13,(36)(37)(38). We found that no promotive effect of TNF-␣ on osteoclastogenesis is observed in the early phase of differentiation in which these molecules are activated.…”

Section: Discussionmentioning

confidence: 99%

Pathological role of osteoclast costimulation in arthritis-induced bone loss

Ochi

Shirakawa²,

Sato

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

102

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Tumor necrosis factor-α cooperates with receptor activator of nuclear factor κB ligand in generation of osteoclasts in stromal cell-depleted rat bone marrow cell culture

Cited by 117 publications

References 54 publications

Osteoclast differentiation antigen, distinct from receptor activator of nuclear factor kappa B, is involved in osteoclastogenesis under calcitonin-regulated conditions

Osteoclast differentiation antigen, distinct from receptor activator of nuclear factor kappa B, is involved in osteoclastogenesis under calcitonin-regulated conditions

IL‐23 promotes osteoclast formation by up‐regulation of receptor activator of NF‐κB (RANK) expression in myeloid precursor cells

Pathological role of osteoclast costimulation in arthritis-induced bone loss

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