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Enhanced expression of interleukin-6, matrix metalloproteinase-13, and receptor activator of NF-κB ligand in cells derived from osteoarthritic subchondral bone

  • Original Article
  • Published:
Journal of Orthopaedic Science

Abstract

Background

The aim of this study was to clarify the significance of subchondral bone in the pathology of osteoarthritis (OA) by investigating the expression of inflammatory cytokines, proteases, and receptor activator of NF-κB ligand (RANKL)/receptor activator of NF-κB (RANK)/osteoprotegerin (OPG) involved in cartilage degeneration.

Methods

Subchondral bone was obtained from 19 patients diagnosed with knee OA and 4 patients diagnosed with femoral neck fracture. Subchondral bone osteoblasts (SBOs) were isolated, and total RNA was extracted. Messenger RNA expression of inflammatory cytokines, proteases, and RANKL/RANK/OPG were analyzed using a real-time reverse transcription-polymerase chain reaction (RT-PCR).

Results

Real-time RT-PCR showed that mRNA expressions of interleukin-6 (IL-6), matrix metalloproteinase-13 (MMP-13), and RANKL were significantly enhanced in OA SBOs compared to SBOs without OA. The expressions of these genes was greater in patients with severe cartilage damage than in those with mild cartilage damage. A high correlation between mRNA expression of IL-6 and that of MMP-13 was found in OA SBOs.

Conclusion

The increases in IL-6, MMP-13, and RANKL expression in OA SBOs suggest that in subchondral bone OA progression involves abnormal osseous tissue remodeling, which induces mechanical property changes. Cartilage degeneration in OA may also be due, at least in part, to IL-6 and MMP-13 produced by SBOs. Comprehensive research on these pathological features may lead to the development of more effective therapies for OA by administration of molecules that affect bone remodeling and metabolism.

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Authors and Affiliations

  1. Department of Orthopaedics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan

    Kei Sakao, Kenji A. Takahashi, Yuji Arai, Hitoshi Tonomura, Atsuo Inoue, Masazumi Saito, Mikihiro Fujioka, Hisatake Takamiya & Toshikazu Kubo

  2. Department of Microbiology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan

    Osam Mazda & Jiro Imanishi

Authors
  1. Kei Sakao
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  2. Kenji A. Takahashi
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  3. Osam Mazda
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  4. Yuji Arai
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  5. Hitoshi Tonomura
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  6. Atsuo Inoue
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  7. Masazumi Saito
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  11. Toshikazu Kubo
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Sakao, K., Takahashi, K.A., Mazda, O. et al. Enhanced expression of interleukin-6, matrix metalloproteinase-13, and receptor activator of NF-κB ligand in cells derived from osteoarthritic subchondral bone. J Orthop Sci 13, 202–210 (2008). https://doi.org/10.1007/s00776-008-1227-5

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  • DOI: https://doi.org/10.1007/s00776-008-1227-5

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