Alpha-mangostin suppresses receptor activator nuclear factor-κB ligand-induced osteoclast formation and bone resorption in RAW264.7 cells by inhibiting the extracellular signal-regulated kinase and c-Jun N-terminal kinase signaling

2018 ◽  
Vol 14 (56) ◽  
pp. 390
Author(s):  
Yong-Hua Li ◽  
Rong-Hua Hong ◽  
Yi-Min Liang ◽  
Han-Song Pan ◽  
Zhao-Hui Cheng
Keyword(s):  
Bone Resorption ◽  
Nuclear Factor Κb ◽  
Osteoclast Formation ◽  
Raw264.7 Cells ◽  
Nuclear Factor ◽  
Kinase Signaling ◽  
Extracellular Signal Regulated Kinase ◽  
Extracellular Signal ◽  
Receptor Activator

scholarly journals Overexpression of γ-Glutamyltransferase in Transgenic Mice Accelerates Bone Resorption and Causes Osteoporosis

Endocrinology ◽  
2007 ◽  
Vol 148 (6) ◽  
pp. 2708-2715 ◽  
Author(s):  
Kiyoshi Hiramatsu ◽  
Yutaro Asaba ◽  
Sunao Takeshita ◽  
Yuji Nimura ◽  
Sawako Tatsumi ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Resorption ◽  
Transgenic Mice ◽  
Bone Destruction ◽  
Nuclear Factor Κb ◽  
Osteoclast Formation ◽  
Expression Cloning ◽  
Nuclear Factor ◽  
Receptor Activator

We previously identified γ-glutamyltransferase (GGT) by expression cloning as a factor inducing osteoclast formation in vitro. To examine its pathogenic role in vivo, we generated transgenic mice that overexpressed GGT in a tissue-specific manner utilizing the Cre-loxP recombination system. Systemic as well as local production of GGT accelerated osteoclast development and bone resorption in vivo by increasing the sensitivity of bone marrow macrophages to receptor activator of nuclear factor-κB ligand, an essential cytokine for osteoclastogenesis. Mutated GGT devoid of enzyme activity was as potent as the wild-type molecule in inducing osteoclast formation, suggesting that GGT acts not as an enzyme but as a cytokine. Recombinant GGT protein increased receptor activator of nuclear factor-κB ligand expression in marrow stromal cells and also stimulated osteoclastogenesis from bone marrow macrophages at lower concentrations. Thus, GGT is implicated as being involved in diseases characterized by accelerated osteoclast development and bone destruction and provides a new target for therapeutic intervention.

scholarly journals Ferryl Hemoglobin Inhibits Osteoclastic Differentiation of Macrophages in Hemorrhaged Atherosclerotic Plaques

2020 ◽  
Vol 2020 ◽  
pp. 1-17
Author(s):  
Erzsébet Zavaczki ◽  
Tamás Gáll ◽  
Abolfazl Zarjou ◽  
Zoltán Hendrik ◽  
László Potor ◽  
...  
Keyword(s):  
Bone Resorption ◽  
Carotid Arteries ◽  
Raw264.7 Cells ◽  
Calcium Deposition ◽  
Atherosclerotic Plaques ◽  
Nuclear Factor ◽  
Nuclear Factor Kappa ◽  
Receptor Activator ◽  
Osteoclastic Differentiation ◽  
Human Carotid

Intraplaque hemorrhage frequently occurs in atherosclerotic plaques resulting in cell-free hemoglobin, which is oxidized to ferryl hemoglobin (FHb) in the highly oxidative environment. Osteoclast-like cells (OLCs) derived from macrophages signify a counterbalance mechanism for calcium deposition in atherosclerosis. Our aim was to investigate whether oxidized hemoglobin alters osteoclast formation, thereby affecting calcium removal from mineralized atherosclerotic lesions. RANKL- (receptor activator of nuclear factor kappa-Β ligand-) induced osteoclastogenic differentiation and osteoclast activity of RAW264.7 cells were studied in response to oxidized hemoglobin via assessing bone resorption activity, expression of osteoclast-specific genes, and the activation of signalization pathways. OLCs in diseased human carotid arteries were assessed by immunohistochemistry. FHb, but not ferrohemoglobin, decreased bone resorption activity and inhibited osteoclast-specific gene expression (tartrate-resistant acid phosphatase, calcitonin receptor, and dendritic cell-specific transmembrane protein) induced by RANKL. In addition, FHb inhibited osteoclastogenic signaling pathways downstream of RANK (receptor activator of nuclear factor kappa-Β). It prevented the induction of TRAF6 (tumor necrosis factor (TNF) receptor-associated factor 6) and c-Fos, phosphorylation of p-38 and JNK (c-Jun N-terminal kinase), and nuclear translocation of NFκB (nuclear factor kappa-Β) and NFATc1 (nuclear factor of activated T-cells, cytoplasmic 1). These effects were independent of heme oxygenase-1 demonstrated by knocking down HO-1 gene in RAW264.7 cells and in mice. Importantly, FHb competed with RANK for RANKL binding suggesting possible mechanisms by which FHb impairs osteoclastic differentiation. In diseased human carotid arteries, OLCs were abundantly present in calcified plaques and colocalized with regions of calcium deposition, while the number of these cells were lower in hemorrhagic lesions exhibiting accumulation of FHb despite calcium deposition. We conclude that FHb inhibits RANKL-induced osteoclastic differentiation of macrophages and suggest that accumulation of FHb in a calcified area of atherosclerotic lesion with hemorrhage retards the formation of OLCs potentially impairing calcium resorption.

Sign in / Sign up

Export Citation Format

Share Document