UNIST, Abnormal Protein Accumulation Also Harms Joint Health

Not Only Alzheimer’s and Huntington’s, but Also Accelerated Cartilage Degeneration

New Arthritis Treatment Strategy Expected by Regulating ERAD System

The research team led by Professor Taeju Park (front row, far right) from the Department of Life Sciences at Ulsan National Institute of Science and Technology (UNIST) discovered that when the function of the ERAD system in chondrocytes declines, cartilage damage worsens.

[Asia Economy Yeongnam Reporting Headquarters Reporter Lee Seryeong] Ulsan National Institute of Science and Technology (UNIST) has discovered that the accumulation of abnormal proteins in cells worsens cartilage damage.

It is commonly known that cartilage is damaged and difficult to regenerate with age, but aging is not the only cause of cartilage weakening.

The research team led by Professor Park Taeju of the Department of Life Sciences at UNIST, in collaboration with Professor Yang Siyoung of Ajou University School of Medicine, conducted a study on cartilage health and proposed a theory that the ERAD system of cartilage cells failing to function properly exacerbates cartilage damage.

The ERAD system (Endoplasmic-reticulum-associated protein degradation) is a metabolic pathway that operates to selectively degrade abnormal proteins through protein degradation related to the endoplasmic reticulum.

An illustration showing cartilage cells with a malfunctioning ERAD system in the endoplasmic reticulum (right) and normal cartilage cells (left).

The research team reported that analysis of cartilage cells from osteoarthritis patients, who suffer from cartilage tissue damage, confirmed a significant decrease in ERAD system gene activity.

This means that proteins necessary for the activation of the ERAD system were not properly synthesized, and similar results were obtained in experiments on mice where the effects of cartilage damage due to aging were excluded.

During the process of cartilage cells synthesizing cartilage tissue proteins, ERAD system gene expression was significantly increased, and frogs in which ERAD system genes were suppressed exhibited severe cartilage hypoplasia.

The ERAD system performs its function inside the cell’s endoplasmic reticulum, and the research team began their study based on the fact that ECM proteins, the main components of cartilage, are also synthesized inside the cartilage cell’s endoplasmic reticulum and secreted outside the cell.

Experimental results revealed that cartilage tissue damage, a major cause of osteoarthritis, can occur due to the decline in ERAD system function along with aging.

The research team suggested a strategy for arthritis treatment and drug development that enhances cartilage cell function by regulating the ERAD system to regenerate damaged cartilage or prevent cartilage damage.

This research was conducted with support from the Korea Research Foundation’s Mid-Career Researcher Support Project and the Innovative New Drug Pipeline Discovery Project, with Dr. Shim Hyojeong of UNIST and doctoral student Cho Chanmi of Ajou University School of Medicine as first authors.

The paper was published on January 21 local time in Science Advances.

The research team stated, “While it has been reported that the accumulation of abnormal proteins in cells is associated with Alzheimer’s disease and Huntington’s disease, we are the first to reveal the relationship between cartilage tissue development, osteoarthritis exacerbation, and the accumulation of abnormal proteins inside cells.”

This content was produced with the assistance of AI translation services.