The relationship between osteoclastogenic and anti-osteoclastogenic pro-inflammatory cytokines differs in human osteoporotic and osteoarthritic bone tissues

Abstract

BackgroundPro-inflammatory cytokines possess osteoclastogenic or anti-osteoclastogenic activities. They influence osteoclasts directly or via the receptor activator of nuclear factor κB (RANK), RANK ligand (RANKL) and osteoprotegerin (OPG) system. Recent evidence suggests that inflammation may play a role in osteoporosis (OP) and osteoarthritis (OA). We aimed therefore to determine whether there is a difference between both groups: first, in the expression of the osteoclastogenic and anti-osteoclastogenic cytokines, second, in correlation of these cytokines with bone mineral density (BMD) and levels of bone turnover markers (BTM) and third, in correlation between the expression of these cytokines and osteoclast specific genes and RANK/RANKL/OPG genes.MethodsHuman bone samples from 54 age and sex matched patients with OP or OA were collected during hip arthroplasty surgery. The expression of 25 genes encoding pro-inflammatory cytokines, their receptors, osteoclast specific genes and RANK/RANKL/OPG genes was measured using quantitative real-time PCR. Total hip, femoral neck and lumbar spine BMD and BTM in blood samples were measured. The comparison between OP and OA was assessed using Student's t-test or Mann-Whitney U test and correlations between gene expression, BMD and BTM were determined using nonparametric correlation.ResultsThe results demonstrated a higher expression of interleukin (IL)-6 and IL-1α in OP, and interferon (IFN)-γ in OA (p < 0.0005). Negative correlations of total hip BMD with tumor necrosis factor-α (TNF-α) in OA and with RANKL/RANK in OP were found (p < 0.05). Significant correlations with BTM were shown for IL-1α and IFN-γ in OP (rho = 0.608 and -0.634) and for TNF-α, IL-6 and transforming growth factor-β1 (TGF-β1) in OA (rho = 0.591, -0.521 and 0.636). Results showed OP specific negative correlations (IFN-γ with ITGB3, IFN-β1 with CTSK, tartrate resistant acid phosphatase (TRAP), CALCR, RANK, RANKL, IL-1α with CTSK, OPG, IL-17A with CALCR) and positive (TGF-β1 with CTSK, TRAP, RANK), and OA specific negative (IL-1α with osteoclast associated immunoglobulin-like receptor (OSCAR), TNF-α with RANK, RANKL, OPG) and positive (IL-6 with RANK, RANKL, OPG) correlations.ConclusionsOur results demonstrate that the relationship between osteoclastogenic and anti-osteoclastogenic pro-inflammatory cytokines differs in human OP and OA bone and could present an important factor for characteristics of OP and OA bone phenotypes.

Identifying genes related with rheumatoid arthritis via system biology analysis

“…Among these common DEGs, the upregulated genes MDK (Weckbach et al, 2012) and HLA-DMB (Morel et al, 2004) and the down-regulated genes FABP4 (Andres Cerezo et al, 2013) and BCL6 (Baecklund et al, 2006) have been previously reported to be associated with RA, whereas there is no definite conclusion about the roles of genes TNFRSF11A, RGS19, ADCY1, TRIM14, TK1, APOBEC3G, ITPKC, AMPH, DDIT4, MIR1908, APOD, SFPQ and CITED1 in RA pathogenesis. Similarly, the up-regulated gene TNFRSF11A (Zupan et al, 2012) and down-regulated gene APOD (Tew et al, 2007) have also been regarded as important mediators in OA, whereas there is no explicit conclusion about the roles of genes RGS19, MDK, ADCY1, TRIM14, HLA-DMB, TK1, APOBEC3G, ITPKC, AMPH, DDIT4, MIR1908, FABP4, SFPQ, CITED1 and BCL6 in the OA pathogenesis. PPI network analysis of the commonly changed genes of OA and RA demonstrates that only genes CXCL12, MMP-1, PPARG and FABP4 constitute lineinteraction, indicating that these genes may form a gene signature of RA and OA and highlighting the importance of further investigating the functional interplay of this gene signature in the pathogenesis of RA and OA.…”

Advanced oxidation protein products decrease the expression of calcium transport channels in small intestinal epithelium via the p44/42 MAPK signaling pathway

“…Three major causative factors are actually recognized: calcium malabsorption, corticosteroid treatment, and inflammation (Bianchi, 2010;Card et al, 2004). More and more results emphasize the role of inflammation (Moschen et al, 2005;Zupan et al, 2012;Agrawal et al, 2011). Because the AOPPs are displayed as pro-inflammatory cytokines in IBD, we expected to identify their accumulation as a new candidate mechanism for IBD-associated bone loss.…”

“…Because the accumulative concentration of plasma AOPPs are closely correlated with the level of dityrosine (a hallmark of oxidized protein), the AOPPs have been considered as a novel marker of oxidant-mediated protein damage (Witko-Sarsat et al, 1996, 1998. Increased levels of AOPPs, which are also closely related to the severity of disease, have recently been found in diabetes (Kalousova et al, 2002;Martin-Gallan et al, 2003;Sebekova et al, 2012), coronary artery disease (Skvarilova et al, 2005), cancer (Kosova et al, 2007;Chang et al, 2008), liver cirrhosis (Zuwala-Jagiello et al, 2011), and chronic inflammatory bowel disease (IBD) (Baskol et al, 2008;Krzystek-Korpacka et al, 2008). This implies that the accumulation of AOPPs may be relevant in mechanisms underlying numerous pathophysiologic conditions.…”

Connecting ribbon and its reaction to acute local inflammation in different organs

“…При цьому діляться переважно клітини фібробластичного ряду. Дефінітивні форми лейкоцитів, макрофа-гів і тучних клітин можуть проліферувати під впливом низки факторів [13][14][15]. Однак у цілому вони не схильні до поділу.…”