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Differentiation of Functional Osteoclasts from Human Peripheral Blood CD14+ Monocytes
Published on: January 27, 2023
MiR-146a-5p Expression in Peripheral CD14⁺ Monocytes from Patients with Psoriatic Arthritis Induces Osteoclast
Shang-Hung Lin1,2,3, Ji-Chen Ho4,5, Sung-Chou Li6
1Department of Dermatology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833, Taiwan. hong51@cgmh.org.tw.
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-α 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.
Insights
MicroRNA-146a-5p (miR-146a-5p) in monocytes drives bone destruction in psoriatic arthritis (PsA). Targeting miR-146a-5p reduces osteoclast activity and correlates with treatment effectiveness in PsA patients.
Area of Science:
- Immunology
- Molecular Biology
- Rheumatology
Background:
- Psoriatic arthritis (PsA) involves bone destruction by monocyte-derived osteoclasts.
- The role of microRNAs (miRNAs) in PsA monocyte function remains largely unexamined.
- Specific miRNAs may regulate osteoclastogenesis in PsA.
Purpose of the Study:
- To investigate the role of specific miRNAs in CD14⁺ monocytes and osteoclasts from PsA patients.
- To determine if these miRNAs contribute to active osteoclastogenesis in PsA.
- To assess the correlation of miRNA expression with disease activity and treatment response.
Main Methods:
- Quantified candidate miRNAs (miR-146a-5p, miR-146b-5p, miR-155-5p) in CD14⁺ monocytes from PsA, psoriasis (PsO), and normal controls (NCs).
- Differentiated monocytes into osteoclasts using TNF-α and RANKL.
- Assessed osteoclast differentiation and bone resorption, and used RNA interference to target miR-146a-5p.
Main Results:
- miR-146a-5p expression was significantly higher in PsA patient monocytes compared to PsO and NCs.
- Osteoclasts derived from PsA patients showed enhanced activation and bone resorption, which was reduced by miR-146a-5p inhibition.
- miR-146a-5p levels decreased in PsA patients after successful biologic treatment, correlating with reduced C-reactive protein (CRP).
Conclusions:
- miR-146a-5p in CD14⁺ monocytes is upregulated in PsA patients and promotes osteoclast activation and bone resorption.
- miR-146a-5p expression serves as a potential biomarker for clinical efficacy in PsA treatment.
- Targeting miR-146a-5p may offer a therapeutic strategy for managing bone destruction in PsA.
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