Nuclear factor-κB pathway activation and phosphatase and tensin homolog downregulation in psoriasis

2015 ◽  
Vol 174 (2) ◽  
pp. 433-435 ◽  
Author(s):  
K.-K. Hong ◽  
M.-J. Gwak ◽  
J. Song ◽  
N.-I. Kim
Keyword(s):  
Nuclear Factor Κb ◽  
Nuclear Factor ◽  
Phosphatase And Tensin Homolog ◽  
Tensin Homolog ◽  
Pathway Activation

scholarly journals Erratum to: Hyperglycemia Exacerbates Burn-Induced Liver Inflammation via Noncanonical Nuclear Factor-κB Pathway Activation

2012 ◽  
Vol 18 (6) ◽  
pp. 1042-1042
Author(s):  
Gabriela A Kulp ◽  
Ronald G. Tilton ◽  
David N Herndon ◽  
Marc G Jeschke
Keyword(s):  
Nuclear Factor Κb ◽  
Nuclear Factor ◽  
Liver Inflammation ◽  
Pathway Activation

scholarly journals Loss of phosphatase and tensin homolog (PTEN) in myeloid cells controls inflammatory bone destruction by regulating the osteoclastogenic potential of myeloid cells

2013 ◽  
Vol 74 (1) ◽  
pp. 227-233 ◽  
Author(s):  
Stephan Blüml ◽  
Martin Friedrich ◽  
Tobias Lohmeyer ◽  
Emine Sahin ◽  
Victoria Saferding ◽  
...  
Keyword(s):  
Myeloid Cells ◽  
Bone Destruction ◽  
Precursor Cells ◽  
Nuclear Factor ◽  
Phosphatase And Tensin Homolog ◽  
Tensin Homolog ◽  
Inflammatory Conditions ◽  
Local Bone

ObjectiveLocal bone destruction in rheumatic diseases, which often leads to disability and severely reduced quality of life, is almost exclusively mediated by osteoclasts. Therefore, it is important to understand pathways regulating the generation of osteoclasts. Here, we analysed the impact of the Phosphoinositide-3-Kinase (PI3K)/Phosphatase and tensin homolog (PTEN) axis on osteoclast generation and bone biology under basal and inflammatory conditions.MethodsWe analysed osteoclastogenesis of wildtype (wt) and PTEN−/− cells in vitro and in vivo, pit resorption and qPCR of osteoclasts in vitro. Mice with a myeloid cell-specific deletion of PTEN and wt littermate mice were investigated by bone histomorphometry and clinical and histological assessment in the human tumour necrosis factor (TNF)-transgenic (hTNFtg) arthritis model.ResultsWe show that myeloid-specific PTEN−/− mice display increased osteoclastogenesis in vitro and in vivo compared to wt mice. Loss of PTEN did not affect the generation or survival of osteoclast precursor cells. However, PTEN deficiency greatly enhanced receptor activator of nuclear factor κ-B ligand (RANKL)-induced expression of the master transcription factor of osteoclastogenesis, nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1), resulting in markedly increased terminal differentiation of osteoclasts in vitro. We also observed increased osteoclastogenesis under inflammatory conditions in the hTNFtg mouse model of arthritis, where hTNFtg/myeloid-specific PTEN−/− mice displayed enhanced local bone destruction as well as osteoclast formation in the inflamed joints. The extent of synovial inflammation, however, as well as recruitment of osteoclast precursor cells was not different between wt and myeloid-specific PTEN−/− mice.ConclusionsThese data demonstrate that loss of PTEN and, therefore, sustained PI3-Kinase signalling in myeloid cells especially, elevates the osteoclastogenic potential of myeloid cells, leading to enhanced inflammatory local bone destruction. Therefore, although our study allows no direct translational conclusion since we used a conditional knockout approach, the therapeutic targeting of the PI3-Kinase pathway may be of benefit in preventing structural joint damage.

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