TY - JOUR
T1 - Metal ions induce bone-resorbing cytokine production through the redox pathway in synoviocytes and bone marrow macrophages
AU - Niki, Yasuo
AU - Matsumoto, Hideo
AU - Suda, Yasunori
AU - Otani, Toshiro
AU - Fujikawa, Kyosuke
AU - Toyama, Yoshiaki
AU - Hisamori, Noriyuki
AU - Nozue, Akira
N1 - Funding Information:
We thank the late Professor Masayuki Shinmei (Department of Orthopaedic Surgery, National Defense Medical College) for planning this work. This work was supported in part by a grant from the Ministry of Education, Science, and Culture of Japan (Grant 12770800).
PY - 2003/4
Y1 - 2003/4
N2 - To evaluate the biological reactions to metal ions potentially released from prosthetic implants, we examined the ability of metal ions to produce bone-resorbing cytokines and the underlying mechanism using synoviocytes and bone marrow (BM) macrophages. The cells were incubated with NiCl2, CoCl2, CrCl3 or Fe2(SO4)3 at optimal concentrations, which are detectable in joint fluid following total joint arthroplasty. The production of interleukin-1β, interleukin-6 and tumor necrosis factor-α were enhanced by all metal ions tested as determined by enzyme-linked immunosorbent assay. From the results of electrophoresis mobility shift assay, all metal ions enhanced the DNA-binding activity of nuclear factor κB (NF-κB), and p50-p65 heterodimers and p50 homodimers were the major subunits. These effects of the metal ions were considerably blocked by pyrrolidine dithiocarbamate (PDTC) known as a radical scavenger. An electron spin resonance study clearly demonstrated the ability of metal ions to generate activated oxygen species (AOS), especially hydroxyl radicals (·OH), which accounts for PDTC-blockade of metal ion-induced NF-κB activation and subsequent cytokine production. Taken together, our data raised the possibility that small amounts of metal ions released from prosthetic implants activate synoviocytes and BM macrophages through the AOS-mediated process (i.e. the redox pathway), and contribute to the initiation of osteolysis at the bone-implant interface.
AB - To evaluate the biological reactions to metal ions potentially released from prosthetic implants, we examined the ability of metal ions to produce bone-resorbing cytokines and the underlying mechanism using synoviocytes and bone marrow (BM) macrophages. The cells were incubated with NiCl2, CoCl2, CrCl3 or Fe2(SO4)3 at optimal concentrations, which are detectable in joint fluid following total joint arthroplasty. The production of interleukin-1β, interleukin-6 and tumor necrosis factor-α were enhanced by all metal ions tested as determined by enzyme-linked immunosorbent assay. From the results of electrophoresis mobility shift assay, all metal ions enhanced the DNA-binding activity of nuclear factor κB (NF-κB), and p50-p65 heterodimers and p50 homodimers were the major subunits. These effects of the metal ions were considerably blocked by pyrrolidine dithiocarbamate (PDTC) known as a radical scavenger. An electron spin resonance study clearly demonstrated the ability of metal ions to generate activated oxygen species (AOS), especially hydroxyl radicals (·OH), which accounts for PDTC-blockade of metal ion-induced NF-κB activation and subsequent cytokine production. Taken together, our data raised the possibility that small amounts of metal ions released from prosthetic implants activate synoviocytes and BM macrophages through the AOS-mediated process (i.e. the redox pathway), and contribute to the initiation of osteolysis at the bone-implant interface.
KW - Activated oxygen species
KW - Bone-resorbing cytokines
KW - Macrophages
KW - Metal ions
KW - Redox pathway
KW - Synoviocytes
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U2 - 10.1016/S0142-9612(02)00531-8
DO - 10.1016/S0142-9612(02)00531-8
M3 - Article
C2 - 12527286
AN - SCOPUS:0037376508
VL - 24
SP - 1447
EP - 1457
JO - Biomaterials
JF - Biomaterials
SN - 0142-9612
IS - 8
ER -