Osteoclasts, mononuclear phagocytes, and c-Fos: new insight into osteoimmunology

Matsuo, Koichi; Ray, Neelanjan

doi:10.2302/kjm.53.78

Cited by 41 publications

(44 citation statements)

References 49 publications

(7 reference statements)

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“…4B,D). FOS is thought to be a proto-oncogene which can enhance motility and invasiveness of cancer cells (Milde-Langosch, 2005) and is frequently activated in a diverse range of cell types (Matsuo and Ray, 2004). Overexpression of c-Fos has been shown to inhibit maturation of myeloblastic leukemia cells (Obata et al, 2003).…”

Section: Discussionmentioning

confidence: 99%

“…However, studies have shown that, in gastric cancer, FOS overexpression occurs in the early stage of tumorigenesis (Yang et al, 2003), but is lost during tumor progression (Jin et al, 2007), indicating that FOS may play its oncogenetic role at the onset of cancer, during which TWIST acts as an EMT promoter. Heterodimers of c-Fos and c-Jun, which are called AP-1, are transcription factors that regulate the expression of a wide variety of genes by binding to their promoters (Matsuo and Ray, 2004). One target of AP-1 is vimentin, which is transcriptionally up-regulated by AP-1 expression (Andreolas et al, 2008) and is involved in the EMT process following TWIST activation (Kang and Massague, 2004).…”

Section: Discussionmentioning

confidence: 99%

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Gene Expression Profiling in TWIST‐Depleted Gastric Cancer Cells

Feng

Wang

Shi

et al. 2008

The Anatomical Record

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TWIST is an important transcription factor during embryonic development and has recently been found to promote the epithelial-mesenchymal transition (EMT) phenomenon seen during the initial steps of tumor metastasis. To further investigate the potential targets and interacting genes of TWIST in human gastric cancer, we performed microarray analysis to compare the gene expression profiles in HGC-27 cells, with or without small interfering RNA (siRNA)-mediated depletion of TWIST. Our results showed that NF1, RAP1A, SRPX, RBL2, PFDN4, ILK, F2R, ERBB3, and MYB were up-regulated, whereas AKR1C2, FOS, GDF15, NR2F1, ATM, and CTPS were down-regulated after TWIST depletion. Moreover, TWIST-depleted HGC-27 cells showed a reversal of the morphologic and molecular changes associated with EMT. These results provide evidence that TWIST regulates the expression of several genes involved in the differentiation, adhesion, and proliferation of gastric cancer cells. The role of TWIST in the development of certain types of gastric cancer is discussed. Anat Rec, 292:262-270, 2009Rec, 292:262-270, . 2008 Wiley-Liss, Inc.Key words: TWIST; siRNA; epithelial-mesenchymal transition; gastric cancer; microarray Epithelial-mesenchymal transition (EMT) is pivotal for morphogenesis and in the transformation of early stage tumors into invasive malignancies (Kang and Massague, 2004). Cells undergoing EMT-characterized by the loss of cell polarity, cell-basement membrane adhesion, and cell-cell contacts-lose expression of epithelial markers (such as E-cadherin and catenin) and acquire expression of mesenchymal components (such as vimentin, fibronectin, and N-cadherin). Recent studies have shown that TWIST is one of the main regulatory proteins that promote EMT and the metastatic phenotype of cells (Karreth and Tuveson, 2004). Increased levels of TWIST are found in a wide range of cancers and are positively correlated with tumor aggressiveness and poor survival rates (Yang et al., 2004), suggesting a general role for TWIST in cancer development.TWIST is a basic helix-loop-helix (bHLH) transcription regulator that can form homodimers or heterodimers with partners that also contain an HLH domain. Depending on the protein partners in the dimers, these complexes play distinct roles in regulating the expression of downstream genes, acting either as activators or repressors. For example, TWIST homodimers can bind to the E-box of the E-cadherin promoter, repressing its expression, whereas their binding to the E-box of the Akt2 gene enhances its expression (Cheng et al

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Gene Expression Profiling in TWIST‐Depleted Gastric Cancer Cells

Feng

Wang

Shi

et al. 2008

The Anatomical Record

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“…mice, but not in c-fos Ϫ/Ϫ mice during osteoclast differentiation (Takayanagi et al, 2002;Matsuo and Ray, 2004;. As a component of the AP-1 transcription factor, c-Fos was suggested to regulate the NFATc1 induction by RANKL (Takayanagi et al, 2002;Matsuo and Ray, 2004;. We therefore examined whether DMS could interfere with the c-Fos regulation by RANKL.…”

Section: Dms Had No Effect On Rankl-induced Nf-b Activationmentioning

confidence: 98%

Suppression of Osteoclastogenesis by N,N-Dimethyl-D-erythro-sphingosine: A Sphingosine Kinase Inhibition-Independent Action

et al. 2007

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N,N-Dimethyl-D-erythro-sphingosine (DMS) competitively inhibits sphingosine kinase (SPHK) and has been widely used to assess the role of SPHK during cellular events, including motility, proliferation, and differentiation. In the present study, the effect of DMS on the differentiation of bone marrow macrophages (BMMs) to osteoclasts was investigated. When the osteoclast precursor cells were treated with DMS, the receptor activator of nuclear factor B ligand (RANKL)-induced osteoclastogenesis was completely blocked. We were surprised to find, however, that knock-down of SPHK by small interfering RNA (siRNA) in BMMs did not reduce osteoclastogenesis. Furthermore, both overexpression of SPHK and exogenous addition of sphingosine-1-phosphate, the product of SPHK activity, failed to overcome the antiosteoclastogenic effect of DMS. These results suggest that DMS inhibited osteoclastogenesis independently of SPHK. Subsequent characterization of the DMS-mediated suppression of osteoclastogenesis revealed that DMS did not affect RANKL-induced activation of JNK, p38, NF-B, and Ca 2ϩ oscillation. On the other hand, DMS strongly inhibited two separate signaling pathways, the RANKL-induced activation of ERK and Akt, which eventually converged on the transcription factors c-Fos and NFATc1. There was significant increase in the osteoclast formation in the presence of DMS when BMMs were overexpressed with c-Fos, suggesting that c-Fos was a critical downstream target of DMS for the inhibition of osteoclastogenesis. Taken together, our data demonstrate that DMS has an antiosteoclastogenic function independently of its SPHK inhibitory activity. Considering previously reported anticancer properties of DMS, our study may also propose that DMS is an ideal drug candidate for bone metastases, for which osteoclastic bone-resorption is crucial.Bone is a complex tissue composed of several cell types. The functions of bone are accomplished by continuous tissue renewal, termed "bone remodeling," occurring throughout life in the adult skeleton. The two major cell types responsible for bone remodeling are osteoclasts and osteoblasts. The harmony between osteoclastic bone resorption and osteoblastic bone formation maintains skeletal homeostasis in adults (Walsh et al., 2006). In pathological bone resorption, this balance is tipped in favor of osteoclast formation, as seen in postmenopausal osteoporosis, autoimmune arthritis, periodontitis, and Paget's disease. Osteoclasts, the only type of cells responsible for bone resorption, are highly specialized cells originating from monocyte/macrophage lineage precursors. The single most important cytokine in the development of osteoclasts is receptor activator of nuclear factor B ligand (RANKL), whereas macrophage-colony stimulating factor (M-CSF), secreted by osteoblasts, provides the survival sigThis work was supported by the Molecular and Cellular BioDiscovery Research Program (M1-0311-00-0024) and the 21C Frontier Functional Proteomics Project Grant (FPR05C2-280) from the Korea Science and ...

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Section: Introductionmentioning

confidence: 99%

“…RANKL stimulates the mouse macrophage cell line RAW264.7 to differentiate into osteoclasts [18][19][20][21][22] . Rahman et al 18) showed that conjugated linoleic acid inhibits osteoclast differentiation of RAW264.7 cells by modulating RANKL signaling, in which RANK is mediated by TRAF6 and activated by NF-B and c-Jun N-terminal kinase in the osteoclasts. Recent studies have shown that lipopolysaccharide (LPS) and inflammatory cytokines such as tumor necrosis factor-and interleukin-1 regulate osteoclast differentiation and function independently of the RANKL-RANK interaction 19,20) .…”

Section: Introductionmentioning

confidence: 99%

Effects of Hachimi-jio-gan Extract on Intestinal Absorption of Calcium in Ovariectomized Mice and Stimulation of RANKL-induced Osteoclast Differentiation of Raw264.7 Cells by Lipopolysaccharide

Ueda

Kanayama

Yamauchi

et al. 2012

J. Hard Tissue Biology.

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: Osteoporosis is a common metabolic bone disease often affecting postmenopausal women, and various medicines are available that attempt to treat and/or prevent this disease. Hachimi-jio-gan is a traditional oriental (Kampo) medicine used clinically, but it's mode of action is still unknown. In this study, the effects of Hachimi-jio-gan extract on intestinal calcium absorption were evaluated in an osteoporosis model using ovariectomized (OVX) and sham-operated (SHAM) mice by investigating pharmacokinetic parameters in these animals. The ability of Hachimi-jio-gan extract to inhibit lipopolysaccharide-mediated stimulation of osteoclasts in bones using receptor activator of the NF-kB ligand (RANKL)-induced osteoclast differentiation of RAW264.7 cells was also investigated. The metabolic behavior of calcium did not differ between OVX and SHAM mice as the pharmacokinetics of calcium was equivalent after intravenous administration. The absolute bioavailability of calcium indicated that the extent of intestinal calcium absorption in the OVX (10.3%) and SHAM (10.7%) mice was at similar low levels. Hachimi-jio-gan extract potentially improved the intestinal calcium absorption by 1.96-and 1.86-fold, respectively. Hachimi-jio-gan extract further suppressed the potent stimulation of RANKL-induced osteoclast differentiation in RAW264.7 cells. These results suggest that Hachimi-jio-gan extract may be suitable for treatment and prevention of osteoporosis through its ability to increase intestinal calcium absorption and suppress osteoclast differentiation.

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Osteoclasts, mononuclear phagocytes, and c-Fos: new insight into osteoimmunology

Cited by 41 publications

References 49 publications

Gene Expression Profiling in TWIST‐Depleted Gastric Cancer Cells

Gene Expression Profiling in TWIST‐Depleted Gastric Cancer Cells

Suppression of Osteoclastogenesis by N,N-Dimethyl-D-erythro-sphingosine: A Sphingosine Kinase Inhibition-Independent Action

Effects of Hachimi-jio-gan Extract on Intestinal Absorption of Calcium in Ovariectomized Mice and Stimulation of RANKL-induced Osteoclast Differentiation of Raw264.7 Cells by Lipopolysaccharide

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