BREAKING: Scientists Link Metabolic Shift to Osteoarthritis, Opening Door to New Treatments
ATHENS, OH – A research team has uncovered a critical link between cartilage metabolism, aging, and the development of osteoarthritis, possibly paving the way for novel preventative and therapeutic strategies. The study, published in Arthritis & rheumatology, identifies a decline in the protein SIRT5 and a corresponding increase in a process called malonylation as key factors in cartilage damage.
Researchers from Ohio University’s Heritage College of Osteopathic Medicine, the University of Utah, and the Buck Institute for research on Aging found that levels of SIRT5 decrease while malonylation increases in cartilage as both people and animals age. This metabolic shift appears to impair the function of chondrocytes – the cells responsible for maintaining cartilage – ultimately contributing to joint deterioration.
“Understanding how metabolism affects cartilage is a big step forward,” said dr. Shouan Zhu,Osteopathic Heritage Foundation Ralph S.Licklider, D.O., endowed professor and investigator with the Ohio Musculoskeletal and Neurological institute and Diabetes Institute at the Heritage College, who led the study. “This gives us a new way to think about treatments-not just for symptoms, but for the root causes of osteoarthritis.”
The team’s examination involved analyzing both human and mouse cartilage samples. They observed lower SIRT5 levels and higher malonylation in older cartilage. Further experiments using mice fed high-fat diets to simulate obesity revealed that mice lacking SIRT5 experienced significantly worse joint damage compared to control groups.
Interestingly, the effects differed between sexes. Male mice without SIRT5 exhibited more severe cartilage loss and joint pain when on a high-fat diet, while female mice showed some degree of protection, though still experiencing some damage. This suggests a potential sex-specific element to SIRT5’s protective role.
Delving deeper, researchers discovered that SIRT5 deficiency led to a reduction in proteins crucial for cartilage building and an increase in proteins associated with inflammation within chondrocytes. They also found that malonylation disrupts glycolysis, a vital energy production process within cells, slowing down the function of the enzyme GAPDH. This suggests a loss of SIRT5 leads to energy deficiencies in cartilage cells, hindering their ability to remain healthy.
The study also identified a rare genetic mutation in the SIRT5 gene within a family with a history of early-onset, severe osteoarthritis. The mutation, named SIRT5F101L, reduces SIRT5’s effectiveness in removing malonyl groups. Testing this mutated version of SIRT5 in lab-grown cartilage cells confirmed it led to increased malonylation and decreased production of cartilage-building proteins, mirroring the findings in SIRT5-deficient mice.
This revelation suggests the SIRT5F101L mutation may be a direct genetic cause of osteoarthritis in some families.
The research, featured on the cover of Arthritis & Rheumatology, marks one of the first direct links between the SIRT5-malonylation pathway and joint health. Researchers believe that boosting SIRT5 activity or reducing malonylation could represent a promising new avenue for treating or preventing osteoarthritis, especially in aging or obese individuals.
