Targeting extracellular signal-regulated kinase (ERK) signaling has therapeutic implications for inflammatory osteolysis.
The extracellular signal-regulated kinase 1/2 (ERK) pathway, part of the mitogen-activated protein kinase (MAPK) family, is well-known for its role in cell differentiation and proliferation. In the context of osteoclastogenesis, macrophage colony stimulating factor (M-CSF) is an upstream activator of ERK signals for the survival of osteoclast precursors prior to their differentiation into multinucleated osteoclasts. In this study, we demonstrate by using both in vivo and in vitro models that the ERK signaling pathway involves an inflammatory response of various cells mediating osteolysis. Osteoblasts exhibit innate immune response by expressing M-CSF in response to lipopolysaccharide (LPS). LPS induced M-CSF expression is mediated by ERK. The inhibition of ERK signaling attenuated the inflammatory response to LPS both in vivo and in vitro. Thus, the ERK pathway may be a potentially important therapeutic target in the treatment of inflammatory osteolysis.
Seo
Sung Wook
SW
Department of Orthopaedic Surgery, Samsung Medical Center, Sungkyunkwan University, Seoul, South Korea.
Lee
Daniel
D
Minematsu
Hiroshi
H
Kim
Abraham D
AD
Shin
Mike
M
Cho
Samuel K
SK
Kim
Dae Won
DW
Yang
Jay
J
Lee
Francis Y
FY
D000818:Animals; D002460:Cell Line; D016503:Drug Delivery Systems / Q000379:methods*; D005419:Flavonoids / Q000008:administration & dosage; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors / Q000502:physiology*; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D010014:Osteolysis / Q000188:drug therapy / Q000201:enzymology*
D005419:Flavonoids; D018836:Inflammation Mediators; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one