Expression of REDD1 reduced in patients with osteoarthritis

SEATTLE — The expression of REDD1, a regulator of cellular stress responses, is reduced in patients with osteoarthritis compared with young, healthy adults, in whom the chondrocyte is highly expressed, according to recently presented research.

Articular cartilage samples were obtained from healthy donors (mean age: 38 years) and patients with osteoarthritis (OA) undergoing knee replacement surgery (mean age: 71 years). After using a genome-wide transcriptomic analysis to identify the Pl3K/Akt/mTOR pathway as the most dysregulated in OA cartilage, the researchers also obtained and assessed REDD1 function within cultured human articular chondrocytes in an in vitro study.

REDD1 expression was measured from the young, healthy donors and donors with OA using quantitative polymerase chain reaction (qPCR) and immunohistochemistry. Additionally, western blot with anti-REDD1 antibodies, phospho-AKT, AKT, phospho-ERK, ERK, phospho-S6, S6, phospho-4EBP and LC3 were used to measure REDD1 expression, intracellular signaling pathway activation and autophagy among the cultured articular chondrocytes.

Observation of western blot results and analysis showed that REDD1 expression was significantly lower in cartilage in patients with OA compared with healthy knee cartilage, and that loss of REDD1 increased mTOR activity while decreasing autophagy activation.

The results suggested REDD1 may be a key regulator of intracellular chondrocyte signaling and an inhibitor of mTOR activity, according to the researchers. - by Shirley Pulawski

Reference:

Alvarez-Garcia O, et al. Paper #10. Presented at: Osteoarthritis Research Society International World Congress on Osteoarthritis. April 30-May 3, 2015; Seattle.

Disclosure: The researchers report no relevant financial disclosures.