TY - JOUR
T1 - Inflammation, cancer, and bone loss
AU - Abu-Amer, Yousef
N1 - Funding Information:
The conventional paradigm suggests that chronic inflammation aids the development of cancer and that inflammatory factors amplify the action of osteoclast inducers. These actions are frequently mediated by the action of NF-κB and constitute the core for tumor and inflammatory osteolysis. In support of this paradigm, inhibitors of the NF-κB pathway or genetic deletion of members of this family abolished both responses. These approaches clarified that whereas the activation of IKK1 by RANKL/RANK pathway inhibits metastatic repression leading to enhanced metastasis, IKK2 appears to coordinate the inflammatory and osteolytic components. This is supported by studies showing that catalytically inactive IKK1 (IKK1 AA ) and IKK2 (IKK2 AA ) fail to support metastasis and inflammatory osteolysis, respectively (reviewed in [ 37 ]). Furthermore, in breast cancer cells, it was found that NF-κB promotes osteolytic metastasis by inducing osteoclastogenesis in a GM-CSF-dependent mechanism [ 38 •• ].
PY - 2009/8
Y1 - 2009/8
N2 - Skeletal distortions impose grave health disparities with potentially devastating consequences, including bone pain, immobility, and morbidity. Bone erosion is chiefly caused by hyperactive osteoclasts summoned to bone in response to circulating factors produced by tumor and inflammatory cells. Intense research in the past two decades has identified crucial elements and intricate circulatory systems that maintain and exacerbate inflammatory osteolysis. This progress led to better understanding of the mechanisms underlying this response and to developing advanced therapeutic interventions. Nevertheless, the multifactorial causes of inflammatory osteolysis continue to impose a great challenge for these therapies. This article provides an overview of some of the prominent facets contributing to this process.
AB - Skeletal distortions impose grave health disparities with potentially devastating consequences, including bone pain, immobility, and morbidity. Bone erosion is chiefly caused by hyperactive osteoclasts summoned to bone in response to circulating factors produced by tumor and inflammatory cells. Intense research in the past two decades has identified crucial elements and intricate circulatory systems that maintain and exacerbate inflammatory osteolysis. This progress led to better understanding of the mechanisms underlying this response and to developing advanced therapeutic interventions. Nevertheless, the multifactorial causes of inflammatory osteolysis continue to impose a great challenge for these therapies. This article provides an overview of some of the prominent facets contributing to this process.
UR - http://www.scopus.com/inward/record.url?scp=68849094124&partnerID=8YFLogxK
U2 - 10.1016/j.coph.2009.06.007
DO - 10.1016/j.coph.2009.06.007
M3 - Review article
C2 - 19577517
AN - SCOPUS:68849094124
SN - 1471-4892
VL - 9
SP - 427
EP - 433
JO - Current Opinion in Pharmacology
JF - Current Opinion in Pharmacology
IS - 4
ER -