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Updated: Sep 2, 2025

Software-Assisted Quantitative Measurement of Osteoarthritic Subchondral Bone Thickness
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Mitochondrial double-stranded RNAs govern the stress response in chondrocytes to promote osteoarthritis development

Sujin Kim1, Keonyong Lee1, Yong Seok Choi2

  • 1Department of Chemical and Biomolecular Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, South Korea.

Cell Reports
|August 10, 2022
PubMed

Insights

Mitochondrial double-stranded RNA (mt-dsRNA) activates immune responses in osteoarthritis (OA) by engaging PKR and TLR3. Autophagy protects cartilage cells by clearing these stress-induced mt-dsRNAs, suggesting a novel therapeutic target.

Area of Science:

  • Immunology
  • Molecular Biology
  • Rheumatology

Background:

  • Protein kinase R (PKR) is an immune protein activated by double-stranded RNAs (dsRNAs).
  • PKR overactivation is linked to inflammatory degenerative diseases like osteoarthritis (OA), but the specific dsRNA activator is unclear.
  • Innate immune activation plays a role in OA pathogenesis.

Purpose of the Study:

  • To identify the dsRNA activator responsible for PKR overactivation in osteoarthritis.
  • To elucidate the mechanism of innate immune activation by dsRNAs in chondrocytes under OA-eliciting conditions.
  • To investigate the role of autophagy in mitigating mitochondrial stress and PKR activation in OA.

Main Methods:

  • Analysis of mitochondrial dsRNA (mt-dsRNA) expression and localization in chondrocytes.
  • Investigation of mt-dsRNA efflux and extracellular release.
  • Assessment of Toll-like receptor 3 (TLR3) activation.
  • Quantification of mt-dsRNAs in patient synovial fluid and cartilage.
  • Evaluation of autophagy's role in mt-dsRNA clearance and chondrocyte protection.

Main Results:

  • Mitochondrial dsRNA (mt-dsRNA) expression and cytosolic release are increased in chondrocytes under OA-inducing conditions.
  • Extracellular mt-dsRNAs activate Toll-like receptor 3 (TLR3) at the plasma membrane, contributing to innate immune activation.
  • Elevated mt-dsRNA levels were observed in OA patient samples and in a mouse model of OA.
  • Autophagy effectively removes cytosolic mtRNAs, preventing PKR activation and protecting chondrocytes from mitochondrial stress.

Conclusions:

  • Mitochondrial dsRNA (mt-dsRNA) acts as a key activator of innate immunity in osteoarthritis, triggering PKR and TLR3 pathways.
  • Autophagy plays a crucial protective role in OA by clearing mt-dsRNAs and mitigating chondrocyte stress.
  • mt-dsRNAs represent a promising therapeutic target for chondroprotective interventions in osteoarthritis.
Keywords:
CP: Molecular biologyautophagyinnate immune responsemitochondrial double-stranded RNAosteoarthritisprotein kinase R

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