Researchers from Korea Advanced Institute of Science and Technology (KAIST) and Seoul National University Bundang Hospital (SNUBH) said on Wednesday that they discovered a biomarker for osteoarthritis called mitochondrial double-stranded RNA (mt-dsRNA).

Professor Kim Yoo-sik of KAIST’s Department of Biochemical Engineering (center) and his team have discovered an alternative to diagnosing and treating osteoarthritis using mitochondrial double-stranded RNAs (mt-dsRNA).
Professor Kim Yoo-sik of KAIST’s Department of Biochemical Engineering (center) and his team have discovered an alternative to diagnosing and treating osteoarthritis using mitochondrial double-stranded RNAs (mt-dsRNA).

Osteoarthritis occurs when the joint cartilage surrounding the bone is worn out, exposing the bone under the cartilage and causing inflammation of the active fluid membrane leading to pain and deformation.

The research team, led by Professors Kim Yoo-sik of KAIST and Lee Yun-jong of SNUBH, revealed that the substance that promotes cell death by inflammation in damaged cartilage during the development of osteoarthritis is mt-dsRNA.

Double-stranded RNA (dsRNA) induces abnormal immune responses, promoting apoptosis and inflammatory reactions. Overexpression of dsRNA is closely related to various degenerative diseases, so regulation of dsRNA is essential to maintain healthy cells. A typical organ that produces dsRNA in a cell is the mitochondria.

Mitochondria separate self-produced dsRNA from the cytoplasm to prevent exposure to dsRNA and the resulting immune response.

The research team confirmed that when mt-dsRNA is exposed to the outside of the mitochondria in an environment for simulating osteoarthritis built from cartilage cells, it causes an immune response as innate immune response proteins recognize it.

Additionally, they detected more mt-dsRNA in the synovial fluid of osteoarthritis patients compared to the fluid in rheumatoid arthritis and gout patients and increased mt-dsRNA in the cartilage of patients with early osteoarthritis. This led the researchers to propose mt-dsRNA as a biomarker that can diagnose osteoarthritis early.

Furthermore, the researchers suggested mt-dsRNA as a new target substance for osteoarthritis treatment by revealing that autophagy can alleviate symptoms of osteoarthritis by removing mt-dsRNA from the cytoplasm.

"This study verified the specific increase in mt-dsRNA expression in the cartilage of actual osteoarthritis mouse models and patients,” Professor Kim said, "If the mechanism of mt-dsRNA in the development of degenerative diseases is analyzed, including Alzheimer's, where mitochondrial damage is also observed, it will be useful for preparing effective treatment strategies."

The study, “Mitochondrial double-stranded RNAs govern the stress response in chondrocytes to promote osteoarthritis development,” was published in the international journal, Cell Reports.

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