Systemic Inflammation Affects Human Osteocyte-Specific Protein and Cytokine Expression

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• 作者：Janak L. Pathak ; Astrid D. Bakker ; Frank P. Luyten…
• 刊名：Calcified Tissue International
• 出版年：2016
• 出版时间：June 2016
• 年：2016
• 卷：98
• 期：6
• 页码：596-608
• 全文大小：1,130 KB
• 刊物类别：Biomedical and Life Sciences
• 刊物主题：Life Sciences
  Biochemistry
  Endocrinology
  Orthopedics
  Cell Biology
  
• 出版者：Springer New York
• ISSN：1432-0827
• 卷排序：98

文摘

Bone remodeling can be disturbed in active rheumatoid arthritis (RA), possibly as a result of elevated levels of circulating inflammatory cytokines. Osteocyte-specific proteins and cytokines play a vital role in bone remodeling by orchestrating bone formation and/or bone resorption. Therefore, we aimed to investigate the effect of RA-serum or inflammatory cytokines on expression of human osteocyte-specific proteins and cytokines. Human trabecular bone chips were cultured with RA-serum or inflammatory cytokines for 7-days. Live-dead staining was performed to assess cell viability. Gene expression of osteocyte-specific proteins and cytokines was analyzed by qPCR. Immuno-staining was performed for osteocyte-specific markers. Approximately 60 % of the osteocytes on the bone chips were alive at day-7. Cells in or on the bone chips did express the gene for osteocyte markers SOST, FGF23, DMP1, and MEPE, and the cytokines IL-1β, IL-6, and TNFα at day 0 and 7. Active RA-serum treatment enhanced IL-1β, TNFα, SOST, and DKK1 gene expression. IL-1β treatment enhanced IL-1β, TNFα, IL-6, IL-8, FGF23, and SOST gene expression. TNFα treatment enhanced IL-1β, TNFα, IL-6, IL-8, and FGF23 gene expression. IL-8 treatment enhanced TNFα, IL-8, and FGF23 gene expression. A combination of IL-1β, IL-6, and TNFα treatment synergistically upregulated IL-1β, IL-6, and IL-8 gene expression, as well as enhanced TNFα, OPG, SOST, and FGF23, and inhibited DKK1 gene expression. In conclusion, gene expression of human osteocyte-specific proteins and cytokines was affected by RA-serum, and exogenous recombinant cytokines treatment suggesting that osteocytes could provide a new target to prevent systemic inflammation-induced bone loss in RA.KeywordsRheumatoid arthritisInflammationCytokineChemokineOsteocyte signalingBone loss