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MiR-146a-5p Expression in Peripheral CD14? Monocytes from Patients with Psoriatic Arthritis Induces Osteoclast Activation, Bone Resorption, and Correlates with Clinical Response.

ABSTRACT: In psoriatic arthritis (PsA), progressive bone destruction is mediated by monocyte-derived osteoclasts. MicroRNAs (miRNAs) regulate many pathophysiological processes; however, their function in PsA patient monocytes has not been examined. This study aims to address whether specific miRNAs in CD14? monocytes and monocyte-derived osteoclasts cause active osteoclastogenesis in PsA patients. Candidate miRNAs related to monocyte activation (miR-146a-5p, miR-146b-5p and miR-155-5p) were measured in circulatory CD14? monocytes collected from 34 PsA patients, 17 psoriasis without arthritis (PsO) patients, and 34 normal controls (NCs). CD14? monocytes were cultured with media containing TNF-? and RANKL to differentiate into osteoclasts. Osteoclast differentiation and bone resorption were measured by TRAP immunostaining and dentin slice resorption, respectively. The results showed that the miR-146a-5p expression was higher in PsA patient-derived CD14? monocytes compared to PsO and NCs. Activation and bone resorption were selectively enhanced in osteoclasts from PsA patients, but both were abrogated by RNA interference against miR-146a-5p. More importantly, after clinical improvement using biologics, the increased miR-146a-5p expression in CD14? monocytes from PsA patients was selectively abolished, and associated with blood CRP level. Our findings indicate that miR-146a-5p expression in CD14? monocytes derived from PsA patients correlates with clinical efficacy, and induction of osteoclast activation and bone resorption.

SUBMITTER: Lin SH

PROVIDER: S-EPMC6352034 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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MiR-146a-5p Expression in Peripheral CD14⁺ Monocytes from Patients with Psoriatic Arthritis Induces Osteoclast Activation, Bone Resorption, and Correlates with Clinical Response.

Lin Shang-Hung SH Ho Ji-Chen JC Li Sung-Chou SC Chen Jia-Feng JF Hsiao Chang-Chun CC Lee Chih-Hung CH

Journal of clinical medicine 20190117 1

In psoriatic arthritis (PsA), progressive bone destruction is mediated by monocyte-derived osteoclasts. MicroRNAs (miRNAs) regulate many pathophysiological processes; however, their function in PsA patient monocytes has not been examined. This study aims to address whether specific miRNAs in CD14⁺ monocytes and monocyte-derived osteoclasts cause active osteoclastogenesis in PsA patients. Candidate miRNAs related to monocyte activation (miR-146a-5p, miR-146b-5p and miR-155-5p) were measured in ci ...[more]

PMID: 30658492

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Project description:BACKGROUND:Psoriasis and psoriatic arthritis (PsA) are inflammatory associated autoimmune disorders. MicroRNA (miR)-146a plays a crucial role in regulating inflammation. A single nucleotide polymorphism in the miR-146a gene (rs2910164), aberrantly alters its gene expression and linked with the pathogenesis of several disorders, including psoriasis and PsA. In South Africa, psoriasis and PsA are extremely rare in the indigenous African population and most common in both the Indian and Caucasian population. The aim of this study was to investigate whether the miR-146a rs2910164 contributes towards psoriasis and PsA development in South African Indian and Caucasian patients. METHODS:South African Indian (n?=?84) and Caucasian (n?=?32) PsA patients (total n?=?116) and healthy control subjects (Indian: n?=?62 and Caucasian: n?=?38; total n?=?100) were recruited in the study. DNA was extracted from whole blood taken from all subjects, and genotyped for the miR-146a rs2910164 using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Data for laboratory parameters were obtained from pathology reports. The consulting rheumatologist collected all other clinical data. RESULTS:Unstratified data (Caucasians?+?Indians): A significant decrease in C-reactive protein (CRP) levels in PsA patients was observed (CRP monitored at inclusion vs. after 6 months of treatment) (18.95?±?2.81 mg/L vs. 9.68?±?1.32 mg/L, p?=?0.0011). The miR-146a rs2910164 variant C-allele frequency in PsA patients was significantly higher vs. healthy controls (35.78% vs. 26% respectively, p?=?0.0295, OR?=?1.59 95% CI 1.05-2.40). Stratified data (Indians): The variant C-allele frequency in Indian PsA patients was significantly higher vs. healthy Indian controls (35.71% vs. 22.58%, p?=?0.0200, OR?=?1.91 95% CI 1.13-3.22). Stratified data (Caucasians): The variant C-allele frequency distribution between Caucasian PsA patients and healthy Caucasian controls was similar. CONCLUSION:The rs2910164 variant C-allele may play a role in the progression of PsA in the South African Indian population. The main limitation in this study was the small sample size in the case-control cohorts, with a low overall statistical power (post-hoc power analysis?=?19%).

Dataset Information

MiR-146a-5p Expression in Peripheral CD14? Monocytes from Patients with Psoriatic Arthritis Induces Osteoclast Activation, Bone Resorption, and Correlates with Clinical Response.

Publications

MiR-146a-5p Expression in Peripheral CD14⁺ Monocytes from Patients with Psoriatic Arthritis Induces Osteoclast Activation, Bone Resorption, and Correlates with Clinical Response.

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