Downregulation of miR-106b attenuates inflammatory responses and joint damage in collagen-induced arthritis
Yunxia Tao1, Zhirong Wang2, Liangliang Wang1
1Department of Orthopedics, First Affiliated Hospital of Soochow University, Suzhou.
Objective:
miRNAs are small, signal-strand, non-coding RNAs that function in post-transcriptional regulation. We analysed the in vivo effect of miR-106b (miR-106b-5p) on inflammatory bone loss in CIA mice.
Methods:
CIA mice are developed by injecting DAB/1 mice with bovine type II collagen containing Freund's adjuvant and then the in vivo effect of miR-106b is examined. On day 22, mice were given lentiviral negative control, lentiviral-mediated miR-106b mimics or lentiviral-mediated miR-106b inhibitor via orbital injection on a weekly basis. Morphological changes in the ankle joints were assessed via micro-CT and histopathology and cytokine expression levels were examined via immunohistochemical staining, ELISA or flow cytometric analysis. miR-106b and osteoclastic-related gene expression was evaluated via quantitative real-time PCR.
Results:
CIA mice were found to have increased miR-106b expression and CIA-associated bone loss and inflammatory infiltration. miR-106b inhibitor treatment markedly decreased arthritis incidence and attenuated bone destruction and histological severity compared with the control group. Moreover, miR-106b inhibitor treatment suppressed RANK ligand (RANKL) expression, increased osteoprotegerin (OPG) expression and reduced the RANKL:OPG ratio in CIA mice. miR-106b inhibition also significantly decreased inflammatory mediator production in joint sections and reduced serum pro-inflammatory cytokine levels when compared with the control group. Additionally, miR-106b inhibition decreased tartrate-resistant acid phosphatase-positive cell numbers and suppressed murine bone marrow macrophage differentiation.
Conclusion:
These findings indicate that miR-106b inhibition can ameliorate CIA-associated inflammation and bone destruction and thus may serve as a potential therapeutic for human RA treatment.
Insights
MicroRNAs (miRNAs) regulate gene expression. Inhibiting miR-106b in collagen-induced arthritis (CIA) mice reduced inflammation and bone loss, suggesting potential for rheumatoid arthritis (RA) treatment.
Area of Science:
- Molecular Biology
- Immunology
- Rheumatology
Background:
- MicroRNAs (miRNAs) are key regulators of post-transcriptional gene expression.
- Inflammatory bone loss, a hallmark of rheumatoid arthritis (RA), involves complex molecular pathways.
- miR-106b has been implicated in various cellular processes, but its role in inflammatory bone loss remains to be fully elucidated.
Purpose of the Study:
- To investigate the in vivo role of miR-106b in collagen-induced arthritis (CIA)-associated inflammatory bone loss.
- To evaluate the therapeutic potential of targeting miR-106b in a mouse model of arthritis.
Main Methods:
- Collagen-induced arthritis (CIA) was established in mice.
- Lentiviral vectors were used to deliver miR-106b inhibitors or mimics.
- Ankle joint morphology was assessed using micro-CT and histopathology.
- Cytokine expression, osteoclastogenesis, and inflammatory mediators were quantified.
Main Results:
- CIA mice exhibited elevated miR-106b expression, bone loss, and inflammation.
- miR-106b inhibition significantly reduced arthritis incidence, bone destruction, and histological severity.
- Inhibition of miR-106b modulated the RANKL/OPG ratio and decreased pro-inflammatory cytokine levels.
- miR-106b inhibition suppressed osteoclast differentiation and tartrate-resistant acid phosphatase activity.
Conclusions:
- miR-106b inhibition effectively ameliorates inflammation and bone destruction in CIA mice.
- Targeting miR-106b presents a promising therapeutic strategy for rheumatoid arthritis.
Related Concept Videos
01:28Inflammatory Response
Inflammation can be triggered by various stimuli, such as impact, abrasion, chemical irritation, infections, and extreme hot or cold temperatures. These can damage cells and connective tissue fibers,...
01:24T Cell Types and Functions
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
01:20The JAK-STAT Signaling Pathway
01:24Drugs for Treatment of Crohn's Disease in IBD Using Biologic Agents: Anti-TNF
01:16TGF - β Signaling Pathway
01:24Inflammatory Response II: Inflammatory Exudate and Tissue Repair
The typical wound exudate is odorless, transparent, straw-colored, thin, and watery. Exudate, however, can differ depending on the state of wound healing. Likewise, the...