Dataset Information

Effects of Arthrocen, an avocado/soy unsaponifiables agent, on inflammatory mediators and gene expression in human chondrocytes.

ABSTRACT: Osteoarthritis (OA) is a chronic joint disease characterized by pain and stiffness. Recently, there has been great interest in the use of plant-derived compounds and supplements in managing the symptoms of OA. Arthrocen is a plant-based supplement consisting of avocado and soy unsaponifiable extracts in a 1 : 2 ratio. In an effort to unravel the potential mechanisms of its action on the cellular level, we utilized an in vitro assay to study its effects on cultured human chondrocytes. By pairing this assay with protein arrays on inflammatory markers, RNA-Seq with downstream pathway analysis, and lipidomics on eicosanoids, we were able to further define its action at the molecular level. Specifically, we found a role for Arthrocen in attenuating the inflammatory response both at the protein and mRNA level. Furthermore, we discovered that Arthrocen diminished prostaglandin E2 (PGE2) levels in response to an inflammatory trigger. Additionally, unlike traditional COX-2 inhibitors, this response rather specifically attenuated PGE2 levels in the presence of inflammation and without lowering levels of other eicosanoids. This implies that Arthrocen could potentially bring about the reduced pain produced by COX-2 inhibitors without the known side effects of COX-2 inhibition.

SUBMITTER: Goudarzi R

PROVIDER: S-EPMC5292663 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature

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Effects of Arthrocen, an avocado/soy unsaponifiables agent, on inflammatory mediators and gene expression in human chondrocytes.

Goudarzi Ramin R Taylor Jared F JF Yazdi Puya G PG Pedersen Brian A BA

FEBS open bio 20170109 2

Osteoarthritis (OA) is a chronic joint disease characterized by pain and stiffness. Recently, there has been great interest in the use of plant-derived compounds and supplements in managing the symptoms of OA. Arthrocen is a plant-based supplement consisting of avocado and soy unsaponifiable extracts in a 1 : 2 ratio. In an effort to unravel the potential mechanisms of its action on the cellular level, we utilized an <i>in vitro</i> assay to study its effects on cultured human chondrocytes. By p ...[more]

PMID: 28174685

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Project description:Background There are conflicting reports on the impact of soy on breast carcinogenesis. This study examines the effects of soy supplementation on breast cancer-related genes and pathways. Methods Women (n = 140) with early-stage breast cancer were randomized to soy protein supplementation (n = 70) or placebo (n = 70) for 7 to 30 days, from diagnosis until surgery. Adherence was determined by plasma isoflavones: genistein and daidzein. Gene expression changes were evaluated by NanoString inin pre- and post-treatment tumor tissue. Genome-wide expression analysis was performed on post-treatment tissue. Proliferation (Ki67) and apoptosis (Cas3) were assessed by immunohistochemistry. Results Plasma isoflavones rose in the soy group (two-sided Wilcoxon rank-sum test, P < .001) and did not change in the placebo group. In paired analysis of pre- and post-treatment samples, 21 genes (out of 202) showed altered expression (two-sided Student’s t-test, P < .05). Several genes including FANCC and UGT2A1 revealed different magnitude and direction of expression changes between the two groups (two-sided Student’s t-test, P < .05). A high-genistein signature consisting of 126 differentially expressed genes was identified from microarray analysis of tumors. This signature was characterized by overexpression (>2 fold) of cell cycle transcripts, including those which promote cell proliferation, such as FGFR2, E2F5, BUB1, CCNB2, MYBL2, CDK1, and CDC20 (P < .01). Soy intake did not result in statistically significant changes in Ki67 or Cas3. Conclusions Gene expression associated with soy intake and high plasma genistein define a signature characterized by overexpression of FGFR2 and genes that drive cell cycle and proliferation pathways. These findings raise the concerns that in a subset of women soy could adversely affect gene expression in breast cancer. Genome-wide expression analysis was performed on breast cancer tissue from women following treatment with soy (n=28) or placebo (n=23).

Project description:BackgroundBladder pain syndrome (BPS) pathology is poorly understood. Treatment strategies are empirical, with limited efficacy, and affected patients have diminished quality of life.ObjectiveWe examined the hypothesis that inflammatory mediators within the bladder contribute to BPS pathology.Design, setting, and participantsFifteen women with BPS and 15 women with stress urinary incontinence without bladder pain were recruited from Cork University Maternity Hospital from October 2011 to October 2012. During cystoscopy, 5-mm bladder biopsies were taken and processed for gene expression analysis. The effect of the identified genes was tested in laboratory animals.Outcome measures and statistical analysisWe studied the expression of 96 inflammation-related genes in diseased and healthy bladders. We measured the correlation between genes and patient clinical profiles using the Pearson correlation coefficient.Results and limitationsAnalysis revealed 15 differentially expressed genes, confirmed in a replication study. FGF7 and CCL21 correlated significantly with clinical outcomes. Intravesical CCL21 instillation in rats caused increased bladder excitability and increased c-fos activity in spinal cord neurons. CCL21 atypical receptor knockout mice showed significantly more c-fos upon bladder stimulation with CCL21 than wild-type littermates. There was no change in FGF7-treated animals. The variability in patient samples presented as the main limitation. We used principal component analysis to identify similarities within the patient group.ConclusionsOur study identified two biologically relevant inflammatory mediators in BPS and demonstrated an increase in nociceptive signalling with CCL21. Manipulation of this ligand is a potential new therapeutic strategy for BPS.Patient summaryWe compared gene expression in bladder biopsies of patients with bladder pain syndrome (BPS) and controls without pain and identified two genes that were increased in BPS patients and correlated with clinical profiles. We tested the effect of these genes in laboratory animals, confirming their role in bladder pain. Manipulating these genes in BPS is a potential treatment strategy.

Dataset Information

Effects of Arthrocen, an avocado/soy unsaponifiables agent, on inflammatory mediators and gene expression in human chondrocytes.

Publications

Effects of Arthrocen, an avocado/soy unsaponifiables agent, on inflammatory mediators and gene expression in human chondrocytes.

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