ERK signaling regulates macrophage colony-stimulating factor expression induced by titanium particles in MC3T3.E1 murine calvarial preosteoblastic cells.
Periprosthetic osteolysis poses a significant clinical problem for patients who have undergone total joint arthroplastic surgeries. It has been widely recognized that there is a strong correlation between wear particles from orthopedic implants and osteolysis. However, the molecular mechanism underlying osteolysis still remains unclear. Although wear particles interact with a mixed cellular environment, namely macrophages and immune cells, osteoblasts compose the majority of the cell population surrounding orthopedic implants. Osteoblasts are also one of the major sources of receptor activator of nuclear factor-kappa beta (NF-kappaB) ligand (RANKL), a factor necessary for osteoclastogenesis. However, macrophage colony-stimulating factor (M-CSF), another cytokine responsible for preosteoclast proliferation, must also be present with RANKL for osteoclastogenesis to occur. The purpose of our study is to determine the signal transduction pathway by which titanium (Ti) particles, a metallic component of many orthopedic implants, induce M-CSF expression in MC3T3.E1 murine calvarial preosteoblastic cells. Using reverse transcriptase-polymerase chain reaction (RT-PCR) and enzyme- linked immunosorbent assay (ELISA), our study demonstrated that submicron-sized Ti particles induce M-CSF expression via the extracellular signal-regulated kinase (ERK) pathway in a dose-dependent manner. Moreover, inhibition studies showed that a specific ERK inhibitor, PD98059, significantly downregulated M-CSF production. Our results support the hypothesis that submicron-sized Ti particles can induce M-CSF expression in osteoblasts and thus may have a significant role in contributing to the onset of periprosthetic osteolysis.
Department of Orthopedic Surgery, Columbia University, New York, NY 10032, USA.
Sung W
SW
Seo
Daniel
D
Lee
Samuel K
SK
Cho
Abraham D
AD
Kim
Hiroshi
H
Minematsu
Ayse B
AB
Celil Aydemir
Jeffrey A
JA
Geller
William
W
Macaulay
Jay
J
Yang
Francis Young
FY
Lee
Francis
F
Young-In Lee
D000818:Animals; D049109:Cell Proliferation; D016207:Cytokines / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005786:Gene Expression Regulation; D016173:Macrophage Colony-Stimulating Factor / Q000096:biosynthesis*; D051379:Mice; D008954:Models, Biological; D010006:Osteoblasts / Q000378:metabolism*; D053245:RANK Ligand / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D012886:Skull / Q000378:metabolism*; D014025:Titanium / Q000737:chemistry* / Q000378:metabolism
D016207:Cytokines; D004791:Enzyme Inhibitors; D053245:RANK Ligand; D016173:Macrophage Colony-Stimulating Factor; D014025:Titanium; D048049:Extracellular Signal-Regulated MAP Kinases