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.

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.

Related Concept Videos

Osteoclasts in Bone Remodeling01:31

Osteoclasts in Bone Remodeling

Osteoclasts are cells responsible for bone resorption and remodeling. They originate from hematopoietic progenitor cells present in the bone marrow. Numerous progenitor cells fuse to form multinucleated cells, each with 10-20 nuclei. A single osteoclast has a diameter of 150 to 200 µM. These cells have ruffled borders that break down the underlying bone tissue and release minerals such as calcium into the blood in bone resorption. Osteoclasts cling to bones with their ruffled edges during...
4.1K
Correlations02:20

Correlations

Correlation means that there is a relationship between two or more variables (such as ice cream consumption and crime), but this relationship does not necessarily imply cause and effect. When two variables are correlated, it simply means that as one variable changes, so does the other. We can measure correlation by calculating a statistic known as a correlation coefficient. A correlation coefficient is a number from -1 to +1 that indicates the strength and direction of the relationship between...
35.9K
Correlation and Causation01:27

Correlation and Causation

Statistical tests can calculate whether there is a relationship, or correlation, between independent and dependent variables. An indirect relationship of the variables signifies a correlation, while a direct relationship shows causation. If it is determined that no connection exists between the variables, then the correlation is a coincidence.
Correlation versus Causation
If the dependent variable increases or decreases when the independent variable increases, there is a positive or negative...
42.5K
Peripheral Arterial Disease II: Clinical Manifestations and Diagnostic Evaluation01:21

Peripheral Arterial Disease II: Clinical Manifestations and Diagnostic Evaluation

Clinical manifestationsPeripheral Arterial Disease (PAD) manifests through a range of symptoms, from the characteristic intermittent claudication to atypical presentations and severe complications in advanced stages. Intermittent claudication, a hallmark symptom of PAD, presents as exercise-induced muscle pain that typically resolves within minutes of rest. This pain is reproducible and stems from inadequate blood flow, leading to the accumulation of lactic acid produced during anaerobic...
425
Correlation01:09

Correlation

In statistics, two variables are said to be correlated if the values of one variable are associated with the other variable. Depending on the relationship between two variables, correlation can be of three types– positive correlation, negative correlation, and zero correlation.
Two variables, for example, a and b, are said to be positively correlated if both variables move in the same direction. In other words, a positive correlation exists between two variables, a and b, if:
15.1K
Correlation and Regression00:53

Correlation and Regression

In statistics, correlation describes the degree of association between two variables. In the subfield of linear regression, correlation is mathematically expressed by the correlation coefficient, which describes the strength and direction of the relationship between two variables. The coefficient is symbolically represented by 'r' and ranges from -1 to +1. A positive value indicates a positive correlation where the two variables move in the same direction. A negative value suggests a...
3.4K