IL-18 induces apoptosis of adherent bone marrow cells in TNF-α mediated osteoclast formation in synergy with IL-12

An excessive consumption of a high-fat diet (HFD) results in becoming overweight or obese, which triggers a chronic inflammatory condition that is associated with a high white blood cell count. Because of the potential for yerba maté (Ilex paraguariensis) (YM) to impact obesity, this study aimed to investigate the effects of YM consumption on the hematological response and on the production of interleukin (IL)-1α, IL-6, tumor necrosis factor (TNF)-α, and IL-10 by bone marrow cells from Wistar rats fed a HFD. Male Wistar rats were fed a control (CON) or HFD diet for twelve weeks. At the end of this period, the rats received YM (1 g/kg/day body weight) for 4 weeks. After euthanasia, hemograms and myelograms were evaluated, while the bone marrow cells were cultured in the presence or absence of lipopolysaccharide (LPS) to evaluate the production of IL-1α, IL-6, TNF-α, and IL-10. The consumption of YM reduced the body weight, the body adiposity, and the cholesterol levels in HFD-fed rats. Bone marrow cells from the HFD group produced more IL-1α, IL-6, and TNF-α, and less IL-10, when compared to cells from the control group, and YM consumption reduced the IL-1α, IL-6, and TNF-α production by the cells. However, cells from the HFD rats that were stimulated with LPS increased their IL-1α, IL-6, and TNF-α production, but YM consumption did not change this result. In summary, the consumption of YM affects the production of IL-1α, IL-6, and TNF-α by bone marrow cells, promotes weight loss, decreases the number of white blood cells, and significantly improves serum cholesterol level in HFD-fed rats. However, the bone marrow cells from the HFD+YM-fed rats challenged with LPS did not show improvement in the inflammatory response compared to the cells from animals fed only a HFD that were also challenged with LPS.

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Jun Dimerization Protein 2 (JDP2), a Member of the AP-1 Family of Transcription Factor, Mediates Osteoclast Differentiation Induced by RANKL

Journal of Experimental Medicine ◽

10.1084/jem.20021321 ◽

2003 ◽

Vol 197 (8) ◽

pp. 1029-1035 ◽

Cited By ~ 56

Author(s):

Reimi Kawaida ◽

Toshiaki Ohtsuka ◽

Junichi Okutsu ◽

Tohru Takahashi ◽

Yuho Kadono ◽

...

Keyword(s):

Bone Marrow ◽

Bone Marrow Cells ◽

Osteoclast Differentiation ◽

Osteoclast Formation ◽

Raw264.7 Cells ◽

Tartrate Resistant Acid Phosphatase ◽

Gene Promoters ◽

Primary Bone ◽

Primary Bone Marrow ◽

Marrow Cells

Osteoclasts are multinucleated cells that resorb bones, and are derived from hematopoietic cells of the monocyte/macrophage lineage. The receptor activator of NF-κB ligand (RANKL, also called ODF/TRANCE/OPGL) stimulates both osteoclast differentiation from osteoclast progenitors and activation of mature osteoclasts. To identify genes responsible for osteoclast differentiation, we used a molecular indexing technique. Here, we report a clone of one of these genes whose transcription is induced by soluble RANKL (sRANKL) in both the RAW264.7 cells of the mouse macrophage cell line and the mouse primary bone marrow cells. The predicted protein was found to be a mouse homologue of Jun dimerization protein 2 (JDP2), a member of the AP-1 family of transcription factors, containing a basic region-leucine zipper motif. Transient transfection experiments revealed that overexpression of JDP2 leads to activation of both tartrate-resistant acid phosphatase (TRAP) and cathepsin K gene promoters in RAW264.7 cells. Infection of mouse primary bone marrow cells with retroviruses expressing JDP2-facilitated sRANKL-mediated formation of TRAP-positive multinuclear osteoclasts. Importantly, antisense oligonucleotide to JDP2 strongly suppressed sRANKL-induced osteoclast formation of RAW264.7 cells. Our findings suggest that JDP2 may play an important role in the RANK-mediated signal transduction system, especially in osteoclast differentiation.

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Vitamin D antagonist, TEI-9647, inhibits osteoclast formation induced by 1α,25-dihydroxyvitamin D3 from pagetic bone marrow cells

The Journal of Steroid Biochemistry and Molecular Biology ◽

10.1016/j.jsbmb.2004.03.025 ◽

2004 ◽

Vol 89-90 ◽

pp. 331-334 ◽

Cited By ~ 21

Author(s):

Seiichi Ishizuka ◽

Noriyoshi Kurihara ◽

Daishiro Miura ◽

Kazuya Takenouchi ◽

Jillian Cornish ◽

...

Keyword(s):

Bone Marrow ◽

Vitamin D ◽

Bone Marrow Cells ◽

Osteoclast Formation ◽

Dihydroxyvitamin D3 ◽

Pagetic Bone ◽

Marrow Cells

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IL-12- and IL-18-Mediated, Nitric Oxide-Induced Apoptosis in TNF-α-Mediated Osteoclastogenesis of Bone Marrow Cells

Calcified Tissue International ◽

10.1007/s00223-011-9494-0 ◽

2011 ◽

Vol 89 (1) ◽

pp. 65-73 ◽

Cited By ~ 12

Author(s):

Hideki Kitaura ◽

Yuji Fujimura ◽

Masako Yoshimatsu ◽

Haruka Kohara ◽

Yukiko Morita ◽

...

Keyword(s):

Nitric Oxide ◽

Bone Marrow ◽

Bone Marrow Cells ◽

Tnf Α ◽

Induced Apoptosis ◽

Marrow Cells

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THIAZOLIDINEDIONES INHIBIT TNF-α-MEDIATED OSTEOCLAST DIFFERENTIATION OF RAW264.7 MACROPHAGES AND MOUSE BONE MARROW CELLS THROUGH DOWNREGULATION OF NFATc1

Shock ◽

10.1097/shk.0b013e3181cc0738 ◽

2010 ◽

Vol 33 (6) ◽

pp. 662-667 ◽

Cited By ~ 14

Author(s):

Chia-Ron Yang ◽

Chang-Chi Lai

Keyword(s):

Bone Marrow ◽

Bone Marrow Cells ◽

Osteoclast Differentiation ◽

Mouse Bone Marrow ◽

Raw264.7 Macrophages ◽

Tnf Α ◽

Mouse Bone Marrow Cells ◽

Marrow Cells

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Overexpression of tumor necrosis factor (TNF)-α and interferon (IFN)-γ by bone marrow cells from patients with myelodysplastic syndromes

Leukemia ◽

10.1038/sj.leu.2400844 ◽

1997 ◽

Vol 11 (12) ◽

pp. 2049-2054 ◽

Cited By ~ 182

Author(s):

M Kitagawa ◽

I Saito ◽

T Kuwata ◽

S Yoshida ◽

S Yamaguchi ◽

...

Keyword(s):

Bone Marrow ◽

Tumor Necrosis Factor ◽

Myelodysplastic Syndromes ◽

Tumor Necrosis ◽

Bone Marrow Cells ◽

Tnf Α ◽

Ifn Γ ◽

Necrosis Factor ◽

Marrow Cells

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Lysine-specific gingipain promotes lipopolysaccharide- and active-vitamin D3-induced osteoclast differentiation by degrading osteoprotegerin

Biochemical Journal ◽

10.1042/bj20081469 ◽

2009 ◽

Vol 419 (1) ◽

pp. 159-166 ◽

Cited By ~ 29

Author(s):

Rika Yasuhara ◽

Yoichi Miyamoto ◽

Masamichi Takami ◽

Takahisa Imamura ◽

Jan Potempa ◽

...

Keyword(s):

Bone Marrow ◽

Alveolar Bone ◽

Bone Marrow Cells ◽

Osteoclast Differentiation ◽

Cysteine Proteases ◽

Osteoclast Formation ◽

Mouse Bone Marrow ◽

Physiological Concentration ◽

Dihydroxyvitamin D3 ◽

Marrow Cells

Porphyromonas gingivalis is one of the major pathogens of periodontitis, a condition characterized by excessive alveolar bone resorption by osteoclasts. The bacterium produces cysteine proteases called gingipains, which are classified according to their cleavage-site specificity into Kgps (lysine-specific gingipains) and Rgps (arginine-specific gingipains). In the present study we examined the effects of gingipains on osteoclast differentiation. In co-cultures of mouse bone-marrow cells and osteoblasts, formation of multinucleated osteoclasts induced by 1α,25(OH)2D3 (1α,25-dihydroxyvitamin D3) was augmented by Kgp but not by RgpB. A physiological concentration (0.1 nM) of 1α,25(OH)2D3 induced the osteoclast formation in the presence of 100 nM Kgp to an extent comparable with that induced by 10 nM 1α,25(OH)2D3. Kgp also enhanced osteoclastogenesis induced by various microbial components, including lipopolysaccharide. Combined use of Kgp and 1α,25(OH)2D3 or lipopolysaccharide also increased the number of resorption pits developed on dentin slices, indicating that the osteoclasts formed in the presence of Kgp possess bone-resorbing activity. The enhanced osteoclastogenesis by Kgp was correlated with a depletion of osteoprotegerin in co-culture medium and was proteolytic-activity-dependent, since benzyloxycarbonyl-L-phenylalanyl-L-lysylacycloxyketone, an inhibitor of Kgp, completely abolished osteoclastogenesis induced by Kgp. Kgp digested osteoprotegerin, since its recombinant protein was susceptible to degradation by Kgp in the presence of serum. As a result, Kgp did not augment osteoclastogenesis in co-cultures of osteoprotegerin-deficient osteoblasts and bone-marrow cells. In addition, enhanced osteoclastogenesis by Kgp was abolished by an excess amount of recombinant osteoprotegerin. These findings suggest that degradation of osteoprotegerin is one of the mechanisms underlying promotion of osteoclastogenesis by Kgp.

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Enhancement of Repopulation and Hematopoiesis of Bone Marrow Cells in Irradiated Mice by Oral Administration of PG101, a Water-Soluble Extract from Lentinus lepideus

Experimental Biology and Medicine ◽

10.1177/153537020322800616 ◽

2003 ◽

Vol 228 (6) ◽

pp. 759-766 ◽

Cited By ~ 16

Author(s):

Mirim Jin ◽

Hyang Jeon ◽

Hyung Jin Jung ◽

Bongcheol Kim ◽

Sung Seup Shin ◽

...

Keyword(s):

Bone Marrow ◽

Oral Administration ◽

Bone Marrow Cells ◽

Flow Cytometric Analysis ◽

Water Soluble ◽

Soluble Extract ◽

Color Flow ◽

Tnf Α ◽

Water Soluble Extract ◽

Marrow Cells

PG101 is a water-soluble extract from Lentinus lepideus. It is a potential biological response modifier that activates selective cytokines in vitro, mainly by controlling cellular transcription factor NF-κB. Effects of PG101 were tested on bone marrow cells in irradiated mice. Mice were irradiated with a dose of 6 Gy and were given PG101 by gavages daily for 24 days. In PG101-treated mice, the number of colony-forming cells, including colony-forming units (CFU)-granulocytes/macrophages (GM) and erythroid burst-forming units (BFU-E), were increased to almost the levels seen in nonirradiated control as early as 8 days after irradiation. Two-color flow cytometric analysis using antibodies to ER-MP12 and ER-MP20 suggested that in the bone marrow cell population, PG101 increased the number of granulocytes (ER-MP12-20med) and myeloid progenitors (ER-MP12+20+). Analysis of surface c-Kit and Gr-1 proteins in bone marrow cells indicated that PG101 might induce differentiation of progenitor cells to granulocytes and/or proliferation of the committed cells. Lastly, oral administration of PG101 highly increased serum levels of GM-CSF, IL-6, and IL-1β. Interestingly, the level of TNF-α was elevated by irradiation in control mice, but was maintained at the background level in PG101-treated mice, suggesting that PG101 might effectively suppress TNF-α-related pathologic conditions. Our results strongly suggest the great potential of PG101 as an immune enhancer during radiotherapy and/or chemotherapy.

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