title: Systemic Inflammation Affects Human Osteocyte-Specific Protein and Cytokine Expression.
abstract: 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.
authors.affiliation: Department of Oral Cell Biology, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam and VU University Amsterdam, MOVE Research Institute Amsterdam, Amsterdam, The Netherlands. j.pathak@tju.edu.cn.|Skeletal Biology and Engineering Research Center, KU Leuven, Leuven, Belgium. j.pathak@tju.edu.cn.|Department of Molecular and Cellular Pharmacology, School of Pharmaceutical Science and Technology (SPST), Tianjin University, Tianjin, China. j.pathak@tju.edu.cn.
authors.forename: Janak L
authors.initials: JL
authors.lastname: Pathak
authors.affiliation: Department of Oral Cell Biology, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam and VU University Amsterdam, MOVE Research Institute Amsterdam, Amsterdam, The Netherlands.
authors.forename: Astrid D
authors.initials: AD
authors.lastname: Bakker
authors.affiliation: Skeletal Biology and Engineering Research Center, KU Leuven, Leuven, Belgium.
authors.forename: Frank P
authors.initials: FP
authors.lastname: Luyten
authors.affiliation: Skeletal Biology and Engineering Research Center, KU Leuven, Leuven, Belgium.
authors.forename: Patrick
authors.initials: P
authors.lastname: Verschueren
authors.affiliation: Department of Rheumatology, VU University Medical Center, MOVE Research Institute Amsterdam, Amsterdam, The Netherlands.
authors.forename: Willem F
authors.initials: WF
authors.lastname: Lems
authors.affiliation: Department of Oral Cell Biology, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam and VU University Amsterdam, MOVE Research Institute Amsterdam, Amsterdam, The Netherlands.
authors.forename: Jenneke
authors.initials: J
authors.lastname: Klein-Nulend
authors.affiliation: Department of Clinical Chemistry, VU University Medical Center, MOVE Research Institute Amsterdam, Amsterdam, The Netherlands.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Bravenboer
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001172:Arthritis, Rheumatoid / Q000378:metabolism*; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism*; D005260:Female; D000089703:Fibroblast Growth Factor-23; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010011:Osteocytes / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D016207:Cytokines; C000717427:FGF23 protein, human; D000089703:Fibroblast Growth Factor-23
keywords: Bone loss; Chemokine; Cytokine; Inflammation; Osteocyte signaling; Rheumatoid arthritis