Esculetin attenuates receptor activator of nuclear factor kappa-B ligand-mediated osteoclast differentiation through c-Fos/nuclear factor of activated T-cells c1 signaling pathway

2015 ◽  
Vol 461 (2) ◽  
pp. 334-341 ◽  
Author(s):  
Jong Min Baek ◽  
Sun-Hyang Park ◽  
Yoon-Hee Cheon ◽  
Sung-Jun Ahn ◽  
Myeung Su Lee ◽  
...  
Keyword(s):  
T Cells ◽  
Signaling Pathway ◽  
Nuclear Factor Kappa B ◽  
Osteoclast Differentiation ◽  
Nuclear Factor ◽  
Activated T Cells ◽  
Nuclear Factor Kappa ◽  
Receptor Activator

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.

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