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ERK Signaling Regulates Macrophage Colony‐Stimulating Factor Expression Induced by Titanium Particles in MC3T3.E1 Murine Calvarial Preosteoblastic Cells
Author(s) -
SEO SUNG W.,
LEE DANIEL,
CHO SAMUEL K,
KIM ABRAHAM D.,
MINEMATSU HIROSHI,
CELIL AYDEMIR AYSE B.,
GELLER JEFFREY A.,
MACAULAY WILLIAM,
YANG JAY,
YOUNGIN LEE FRANCIS
Publication year - 2007
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1196/annals.1402.027
Subject(s) - rankl , osteolysis , mapk/erk pathway , osteoclast , signal transduction , bone resorption , macrophage colony stimulating factor , cytokine , chemistry , microbiology and biotechnology , growth factor , cancer research , activator (genetics) , macrophage , immunology , medicine , receptor , biology , dentistry , biochemistry , in vitro
: 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‐κB) 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.