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

2004 ◽  
Vol 89-90 ◽  
pp. 331-334 ◽  
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

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

2009 ◽  
Vol 419 (1) ◽  
pp. 159-166 ◽  
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.

scholarly journals The role of gp130-mediated signals in osteoclast development: regulation of interleukin 11 production by osteoblasts and distribution of its receptor in bone marrow cultures.

1996 ◽  
Vol 183 (6) ◽  
pp. 2581-2591 ◽  
Author(s):  
E Romas ◽  
N Udagawa ◽  
H Zhou ◽  
T Tamura ◽  
M Saito ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Cells ◽  
Osteoclast Formation ◽  
Pcr Analysis ◽  
Dihydroxyvitamin D3 ◽  
Bone Marrow Cultures ◽  
Primary Osteoblasts ◽  
Marrow Cultures

Interleukin (IL)-11 is a multifunctional cytokine whose role in osteoclast development has not been fully elucidated. We examined IL-11 production by primary osteoblasts and the effects of rat monoclonal anti-mouse glycoprotein 130 (gp130) antibody on osteoclast formation, using a coculture of mouse osteoblasts and bone marrow cells. IL-1, TNF alpha, PGE2, parathyroid hormone (PTH) and 1 alpha,25-dihydroxyvitamin D3 (1 alpha,25(OH)2D3) similarly induced production of IL-11 by osteoblasts, but IL-6, IL-4, and TGF beta did not. Primary osteoblasts constitutively expressed mRNAs for both IL-11 receptor (IL-11R alpha) and gp130. Osteotropic factors did not modulate IL-11R alpha mRNA at 24 h, but steady-state gp130 mRNA expression in osteoblasts was upregulated by 1 alpha,25(OH)2D3, PTH, or IL-1. In cocultures, the formation of multinucleated osteoclast-like cells (OCLs) in response to IL-11, or IL-6 together with its soluble IL-6 receptor was dose-dependently inhibited by rat monoclonal anti-mouse gp130 antibody. Furthermore, adding anti-gp130 antibody abolished OCL formation induced by IL-1, and partially inhibited OCL formation induced by PGE2, PTH, or 1 alpha,25(OH)2D3. During osteoclast formation in marrow cultures, a sequential relationship existed between the expression of calcitonin receptor mRNA and IL-11R alpha mRNA. Osteoblasts as well as OCLs expressed transcripts for IL-11R alpha, as indicated by RT-PCR analysis and in situ hybridization. These results suggest a central role of gp130-coupled cytokines, especially IL-11, in osteoclast development. Since osteoblasts and mature osteoclasts expressed IL-11R alpha mRNA, both bone-forming and bone-resorbing cells are potential targets of IL-11.

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

2003 ◽  
Vol 197 (8) ◽  
pp. 1029-1035 ◽  
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.

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

2006 ◽  
Vol 107 (1) ◽  
pp. 22-31 ◽  
Author(s):  
Hideki Kitaura ◽  
Mutsuhito Tatamiya ◽  
Noriko Nagata ◽  
Yuji Fujimura ◽  
Toshiko Eguchi ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Cells ◽  
Osteoclast Formation ◽  
Tnf Α ◽  
Marrow Cells

scholarly journals Vitamin K stimulates osteoblastogenesis and inhibits osteoclastogenesis in human bone marrow cell culture

2003 ◽  
Vol 176 (3) ◽  
pp. 339-348 ◽  
Author(s):  
Y Koshihara ◽  
K Hoshi ◽  
R Okawara ◽  
H Ishibashi ◽  
S Yamamoto
Keyword(s):  
Bone Marrow ◽  
Vitamin K ◽  
Stromal Cells ◽  
Bone Marrow Cells ◽  
Osteoclast Formation ◽  
Bone Marrow Culture ◽  
Human Bone ◽  
Human Bone Marrow ◽  
Osteogenic Potential ◽  
Marrow Cells

Accumulating evidence indicates that menaquinone-4 (MK-4), a vitamin K(2) with four isoprene units, inhibits osteoclastogenesis in murine bone marrow culture, but the reason for this inhibition is not yet clear, especially in human bone marrow culture. To clarify the inhibitory mechanism, we investigated the differentiation of colony-forming-unit fibroblasts (CFU-Fs) and osteoclasts in human bone marrow culture, to learn whether the enhancement of the differentiation of CFU-Fs from progenitor cells might relate to inhibition of osteoclast formation. Human bone marrow cells were grown in alpha-minimal essential medium with horse serum in the presence of MK-4 until adherent cells formed colonies (CFU-Fs). Colonies that stained positive for alkaline phosphatase activity (CFU-F/ALP(+)) were considered to have osteogenic potential. MK-4 stimulated the number of CFU-F/ALP(+) colonies in the presence or absence of dexamethasone. The stimulation was also seen in vitamin K(1) treatment. These cells had the ability to mineralize in the presence of alpha-glycerophosphate. In contrast, both MK-4 and vitamin K(1) inhibited 1,25 dihydroxyvitamin D(3)-induced osteoclast formation and increased stromal cell formation in human bone marrow culture. These stromal cells expressed ALP and Cbfa1. Moreover, both types of vitamin K treatment decreased the expression of receptor activator of nuclear factor kappaB ligand/osteoclast differentiation factor (RANKL/ODF) and enhanced the expression of osteoprotegerin/osteoclast inhibitory factor (OPG/OCIF) in the stromal cells. The effective concentrations were 1.0 microM and 10 microM for the expression of RANKL/ODF and OPG/OCIF respectively. Vitamin K might stimulate osteoblastogenesis in bone marrow cells, regulating osteoclastogenesis through the expression of RANKL/ODF more than through that of OPG/OCIF.

scholarly journals Effect of IL-12 on TNF-α-Mediated Osteoclast Formation in Bone Marrow Cells: Apoptosis Mediated by Fas/Fas Ligand Interaction

2002 ◽  
Vol 169 (9) ◽  
pp. 4732-4738 ◽  
Author(s):  
Hideki Kitaura ◽  
Noriko Nagata ◽  
Yuji Fujimura ◽  
Hitoshi Hotokezaka ◽  
Noriaki Yoshida ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Fas Ligand ◽  
Bone Marrow Cells ◽  
Osteoclast Formation ◽  
Ligand Interaction ◽  
Tnf Α ◽  
Marrow Cells
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