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 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.

Expression of IL-6 Receptor and GP130 in Mouse Bone Marrow Cells During Osteoclast Differentiation

Bone ◽  
1998 ◽  
Vol 22 (5) ◽  
pp. 487-493 ◽  
Author(s):  
Y Gao ◽  
I Morita ◽  
N Maruo ◽  
T Kubota ◽  
S Murota ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Cells ◽  
Osteoclast Differentiation ◽  
Mouse Bone Marrow ◽  
Mouse Bone Marrow Cells ◽  
Marrow Cells

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 Interleukin (IL)-6 induction of osteoclast differentiation depends on IL-6 receptors expressed on osteoblastic cells but not on osteoclast progenitors.

1995 ◽  
Vol 182 (5) ◽  
pp. 1461-1468 ◽  
Author(s):  
N Udagawa ◽  
N Takahashi ◽  
T Katagiri ◽  
T Tamura ◽  
S Wada ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Bone Marrow ◽  
Transgenic Mice ◽  
Bone Marrow Cells ◽  
Osteoclast Differentiation ◽  
Osteoclast Formation ◽  
Osteoblastic Cells ◽  
Mouse Bone Marrow ◽  
Spleen Cells ◽  
Normal Spleen

We reported that interleukin (IL) 6 alone cannot induce osteoclast formation in cocultures of mouse bone marrow and osteoblastic cells, but soluble IL-6 receptor (IL-6R) strikingly triggered osteoclast formation induced by IL-6. In this study, we examined the mechanism of osteoclast formation by IL-6 and related cytokines through the interaction between osteoblastic cells and osteoclast progenitors. When dexamethasone was added to the cocultures, IL-6 could stimulate osteoclast formation without the help of soluble IL-6R. Osteoblastic cells expressed a very low level of IL-6R mRNA, whereas fresh mouse spleen and bone marrow cells, both of which are considered to be osteoclast progenitors, constitutively expressed relatively high levels of IL-6R mRNA. Treatment of osteoblastic cells with dexamethasone induced a marked increase in the expression of IL-6R mRNA. By immunoblotting with antiphosphotyrosine antibody, IL-6 did not tyrosine-phosphorylate a protein with a molecular mass of 130 kD in osteoblastic cells but did so in dexamethasone-pretreated osteoblastic cells. Osteoblastic cells from transgenic mice constitutively expressing human IL-6R could support osteoclast development in the presence of human IL-6 alone in cocultures with normal spleen cells. In contrast, osteoclast progenitors in spleen cells from transgenic mice overexpressing human IL-6R were not able to differentiate into osteoclasts in response to IL-6 in cocultures with normal osteoblastic cells. These results clearly indicate that the ability of IL-6 to induce osteoclast differentiation depends on signal transduction mediated by IL-6R expressed on osteoblastic cells but not on osteoclast progenitors.

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