Osteoblasts derived from osteophytes produce interleukin-6, interleukin-8, and matrix metalloproteinase-13 in osteoarthritis |
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Authors: | Kei Sakao Kenji A Takahashi Yuji Arai Masazumi Saito Kuniaki Honjo Nobuyuki Hiraoka Hidetsugu Asada Masaharu Shin-Ya Jiro Imanishi Osam Mazda Toshikazu Kubo |
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Institution: | (1) Department of Orthopaedics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan;(2) Department of Microbiology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan |
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Abstract: | To clarify the significance of the osteophytes that appear during the progression of osteoarthritis (OA), we investigated
the expression of inflammatory cytokines and proteases in osteoblasts from osteophytes. We also examined the influence of
mechanical stress loading on osteoblasts on the expression of inflammatory cytokines and proteases. Osteoblasts were isolated
from osteophytes in 19 patients diagnosed with knee OA and from subchondral bone in 4 patients diagnosed with femoral neck
fracture. Messenger RNA expression and protein production of inflammatory cytokines and proteases were analyzed using real-time
RT-PCR and ELISA, respectively. To examine the effects of mechanical loading, continuous hydrostatic pressure was applied
to the osteoblasts. We determined the mRNA expression and protein production of IL-6, IL-8, and MMP-13, which are involved
in the progression of OA, were increased in the osteophytes. Additionally, when OA pathological conditions were simulated
by applying a nonphysiological mechanical stress load, the gene expression of IL-6 and IL-8 increased. Our results suggested
that nonphysiological mechanical stress may induce the expression of biological factors in the osteophytes and is involved
in OA progression. By controlling the expression of these genes in the osteophytes, the progression of cartilage degeneration
in OA may be reduced, suggesting a new treatment strategy for OA. |
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Keywords: | Osteophytes Osteoarthritis Interleukin-6 Interleukin-8 Matrix metalloproteinase-13 |
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