Zoledronate inhibits receptor activator of nuclear factor kappa-B ligand-induced osteoclast differentiation via suppression of expression of nuclear factor of activated T-cell c1 and carbonic anhydrase 2

2015 ◽  
Vol 60 (4) ◽  
pp. 557-565 ◽  
Author(s):  
Takayuki Nakagawa ◽  
Kouji Ohta ◽  
Kazumi Kubozono ◽  
Yoko Ishida ◽  
Takako Naruse ◽  
...  
Keyword(s):  
T Cell ◽  
Carbonic Anhydrase ◽  
Nuclear Factor Kappa B ◽  
Osteoclast Differentiation ◽  
Nuclear Factor ◽  
Nuclear Factor Kappa ◽  
Receptor Activator ◽  
Activated T Cell

scholarly journals The expression of nuclear factor of activated T cell c1 and receptor activator of nuclear factor kappa β induced by Enterococcus faecalis in osteoclastogenesis (laboratory experiment on Wistar rats)

2019 ◽  
Vol 52 (4) ◽  
pp. 172
Author(s):  
Nirawati Pribadi ◽  
Rosita Rahmawati ◽  
Mandojo Rukmo ◽  
Adelina Kristanti Tandadjaja ◽  
Hendy Jaya Kurniawan ◽  
...  
Keyword(s):  
T Cell ◽  
Enterococcus Faecalis ◽  
Wistar Rats ◽  
Bone Defects ◽  
Control Group ◽  
Nuclear Factor ◽  
Nuclear Factor Kappa ◽  
Endodontic Infection ◽  
Receptor Activator ◽  
Activated T Cell

Background: Enterococcus faecalis (E. faecalis) is the most common bacteria species in persistent endodontic infection of teeth undergoing root canal treatment at a prevalence of 38%. The virulence factor of this bacterium is Lipoteichoic acid (LTA) which can be recognized by Toll-like receptors-4 (TLR-4) that produce a stimulus and provoke an immune response. Inflammation results in bone defects that feature multiple cytokines and interactions between different cell types. Bone loss within a periapical tooth is characterized by osteoclast formation (osteoclastogenesis) in the bone. Purpose: This study aimed to determine the expression of nuclear factor of activated T cell c1 (NFATc1) and receptor activator of nuclear factor kappa β (RANK) which played a role in osteoclastogenesis at different time intervals. Methods: 36 upper molar teeth of the research subjects were induced with 106 CFU Enterococcus faecalis and subsequently observed for 7 and 21 days with the NFATc1 and RANK being counted microscopically at 1000X magnification across 20 viewing fields. Thereafter, the data was examined and analyzed by means of an independent T test using SPSS. Results: NFATc1 and RANK expression were higher in the group including E. faecalis on days 7 and 21 than in the control group. There were significant differences between the treatment group and control group with regard to NFATc1 and RANK expression (p<0.05). Conclusion: The study showed that the expression of NFATc1 and RANK, which plays a role in osteoclastogenesis, was higher in periapical bone defects in Wistar rats induced by E. faecalis than those which were not induced.

The OPG/TRAIL Interaction in an In Vitro Osteoclastogenesis Model Derived from Human Multiple Myeloma-Bone Disease.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2361-2361
Author(s):  
Stefano Molica
Keyword(s):  
Multiple Myeloma ◽  
T Cells ◽  
T Cell ◽  
Bone Disease ◽  
Nuclear Factor Kappa B ◽  
Nuclear Factor ◽  
Nuclear Factor Kappa ◽  
Trail Receptors ◽  
Receptor Activator

Abstract The development of multiple myeloma (MM)-bone disease is mediated by increased recruitment and activity of osteoclasts (OCs). Osteoclastogenesis is regulated by a complex signaling system, that involves receptor activator of nuclear factor-kappa B (RANK), receptor activator of nuclear factor-kappa B ligand (RANKL) and osteoprotegerin (OPG), all belonging to the Tumor Necrosis Factor (TNF) family. The aims of our study were to investigate: the MM T cell involvement in osteoclastogenesis, and the expression of the major osteoclastogenic mediators. Unstimulated and unfractionated peripheral blood mononuclear cells (PBMCs) isolated from 32 MM patients with or without osteolytic bone lesions, and parallel T cell-depleted cultures were used as in vitro osteoclastogenesis models. In addition, unstimulated and unfractionated PBMC cultures from 32 controls with nonneoplastic disease without any skeletal involvement were also established. Our results showed that the OCs derived from MM-bone disease PBMCs spontaneously developed and displayed a longer survival in a T cell-dependent way. Differently in T cell-depleted MM PBMC cultures, the addition of macrophage-colony stimulating factor (M-CSF) and RANKL was necessary to promote the formation of OCs, that however did not exibit a longer survival. MM-bone disease T cells overexpressed RANKL, OPG and TNF-related apoptosis inducing ligand (TRAIL), also detected in large amounts in the culture media. Despite high OPG levels, the persistence of osteoclastogenesis in our system can be related to the interaction between OPG and TRAIL, that were coimmunoprecipitated by a monoclonal antibody (mAb) against TRAIL. The evidence that TRAIL binds to OPG blocking OPG anti-osteoclastogenic effect is also supported by the addition of different concentrations of functional anti-TRAIL mAb, significantly decreasing the OC formation. The OCs developed from MM-bone disease PBMCs expressed a T cell-modulated balance of death and decoy TRAIL receptors. In particular, we found these OCs overexpressed TRAIL decoy receptor DcR2 in the presence of T cells, and death receptor DR4 in the T cell-depleted cultures. In conclusion, our results highlight that MM-bone disease T cells support the spontaneous OC formation with longer survival, involving the OPG/TRAIL interaction and the unbalanced OC expression of TRAIL death and decoy receptors.

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

2001 ◽  
Vol 170 (1) ◽  
pp. 175-183 ◽  
Author(s):  
T Kukita ◽  
A Kukita ◽  
T Watanabe ◽  
T Iijima
Keyword(s):  
Cell Surface ◽  
Nuclear Factor Kappa B ◽  
Osteoclast Differentiation ◽  
Cell Formation ◽  
Nuclear Factor ◽  
Metabolic Bone Diseases ◽  
Escape Phenomenon ◽  
Nuclear Factor Kappa ◽  
Receptor Activator ◽  
Nf Kappab

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-kappaB) 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-kappaB. 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.

scholarly journals Triiodothyronine (T3) does not induce Rankl expression in rat Ros 17/2.8 cells

2008 ◽  
Vol 52 (1) ◽  
pp. 109-113 ◽  
Author(s):  
Patrícia P. Saraiva ◽  
Silvania S. Teixeira ◽  
Célia Regina Nogueira ◽  
Carlos Roberto Padovani
Keyword(s):  
Messenger Rna ◽  
Nuclear Factor Kappa B ◽  
Osteoclast Differentiation ◽  
Hormone Treatment ◽  
Nuclear Factor ◽  
Rankl Expression ◽  
Loss Mechanism ◽  
Nuclear Factor Kappa ◽  
Rankl Mrna ◽  
Receptor Activator

Osteoclastogenesis may be regulated via activation of the RANK/RANKL (receptor activator of nuclear factor-kappa B/ receptor activator of nuclear factor-kappa B ligand) system, which is mediated by osteoblasts. However, the bone loss mechanism induced by T3 (triiodothyronine) is still controversial. In this study, osteoblastic lineage rat cells (ROS 17/2.8) were treated with T3 (10-8 M, 10-9 M, and 10-10 M), and RANKL mRNA (messenger RNA) expression was measured by semiquantitative RT-PCR. Our results show that T3 concentrations used did not significantly enhance RANKL expression compared to controls without hormone treatment. This data suggests that other mechanisms, unrelated to the RANK/RANKL system, might be to activate osteoclast differentiation in these cells.

scholarly journals Yukmijihwang-Tang Suppresses Receptor Activator of Nuclear Factor Kappa-B Ligand (RANKL)-Induced Osteoclast Differentiation and Prevents Ovariectomy (OVX)-Mediated Bone Loss

Molecules ◽  
2021 ◽  
Vol 26 (24) ◽  
pp. 7579
Author(s):  
Sang-Yong Han ◽  
Yun-Kyung Kim
Keyword(s):  
Bone Loss ◽  
Nuclear Factor Kappa B ◽  
Nuclear Translocation ◽  
Transmembrane Protein ◽  
Osteoclast Differentiation ◽  
Bone Diseases ◽  
Tartrate Resistant Acid Phosphatase ◽  
Nuclear Factor ◽  
Nuclear Factor Kappa ◽  
Receptor Activator

Yukmijihwang-tang (YJ) has been used to treat diabetes mellitus, renal disorders, and cognitive impairment in traditional medicine. This study aimed to evaluate the anti-osteoporotic effect of YJ on ovariectomy (OVX)-induced bone loss in a rat and receptor activator of nuclear factor kappa-B ligand (RANKL)-mediated osteoclast differentiation in bone marrow macrophages (BMMs). YJ reduced the formation of tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cells (MNCs) in an osteoclast/osteoblast co-culture system by regulating the ratio of RANKL/osteoprotegerin (OPG) by osteoblasts. Overall, YJ reduced TRAP-positive cell formation and TRAP activity and F-actin ring formation. Analysis of the underlying mechanisms indicated that YJ inhibited the activation of the nuclear factor of activated T cell cytoplasmic 1 (NFATc1) and c-Fos, resulting in the suppression of osteoclast differentiation-related genes such as TRAP, ATPase, H+ transporting, lysosomal 38 kDa, V0 subunit d2, osteoclast-associated receptor, osteoclast-stimulatory transmembrane protein, dendritic cell-specific transmembrane protein, matrix metalloproteinase-9, cathepsin K, and calcitonin receptor. YJ also inhibited the nuclear translocation of NFATc1. Additionally, YJ markedly inhibited RANKL-induced phosphorylation of signaling pathways activated in the early stages of osteoclast differentiation including the p38, JNK, ERK, and NF-κB. Consistent with these in vitro results, the YJ-administered group showed considerably attenuated bone loss in the OVX-mediated rat model. These results provide promising evidence for the potential novel therapeutic application of YJ for bone diseases such as osteoporosis.

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