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Updated: Dec 18, 2025
Differentiation of Functional Osteoclasts from Human Peripheral Blood CD14+ Monocytes
Published on: January 27, 2023
Upregulation of miR-941 in Circulating CD14+ Monocytes Enhances Osteoclast Activation via WNT16 Inhibition in
Shang-Hung Lin1,2,3, Ji-Chen Ho1, Sung-Chou Li4
1Department of Dermatology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan.
Abstract:
Psoriatic arthritis (PsA) is a destructive joint disease mediated by osteoclasts. MicroRNAs (miRNAs) regulate several important pathways in osteoclastogenesis. We profiled the expression of miRNAs in CD14+ monocytes from PsA patients and investigated how candidate microRNAs regulate the pathophysiology in osteoclastogenesis. The RNA from circulatory CD14+ monocytes was isolated from PsA patients, psoriasis patients without arthritis (PsO), and healthy controls (HCs). The miRNAs were initially profiled by next-generation sequencing (NGS). The candidate miRNAs revealed by NGS were validated by PCR in 40 PsA patients, 40 PsO patients, and 40 HCs. The osteoclast differentiation and its functional resorption activity were measured with or without RNA interference against the candidate miRNA. The microRNA-941 was selectively upregulated in CD14+ monocytes from PsA patients. Osteoclast development and resorption ability were increased in CD14+ monocytes from PsA patients. Inhibition of miR-941 abrogated the osteoclast development and function while increased the expression of WNT16. After successful treatment, the increased miR-941 expression in CD14+ monocytes from PsA patients was revoked. The expression of miR-941 in CD14+ monocytes is associated with PsA disease activity. MiR-941 enhances osteoclastogenesis in PsA via WNT16 repression. The miR-941 could be a potential biomarker and treatment target for PsA.
Insights
MicroRNA-941 (miR-941) is upregulated in psoriatic arthritis (PsA) patients, driving osteoclast activity and bone destruction. Inhibiting miR-941 may offer a new therapeutic strategy for PsA.
Area of Science:
- Immunology
- Molecular Biology
- Rheumatology
Background:
- Psoriatic arthritis (PsA) is a joint disease driven by osteoclasts.
- MicroRNAs (miRNAs) play a role in osteoclast formation (osteoclastogenesis).
Purpose of the Study:
- To identify and characterize miRNAs involved in PsA pathophysiology.
- To investigate the role of miR-941 in PsA osteoclastogenesis and its potential as a therapeutic target.
Main Methods:
- miRNA profiling using next-generation sequencing (NGS) in CD14+ monocytes from PsA patients, psoriasis patients (PsO), and healthy controls (HCs).
- Quantitative PCR validation of candidate miRNAs.
- Assessment of osteoclast differentiation and resorption activity with and without miR-941 inhibition.
- Analysis of WNT16 expression.
Main Results:
- MicroRNA-941 (miR-941) was significantly upregulated in CD14+ monocytes of PsA patients compared to PsO and HCs.
- PsA monocytes showed increased osteoclast development and resorption.
- Inhibition of miR-941 reduced osteoclastogenesis and resorption, increasing WNT16 expression.
- miR-941 levels correlated with PsA disease activity and decreased after successful treatment.
Conclusions:
- miR-941 promotes osteoclastogenesis in PsA by repressing WNT16.
- miR-941 is a potential biomarker for PsA disease activity.
- miR-941 represents a promising therapeutic target for psoriatic arthritis.
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