Cold exposure promotes the progression of osteoarthritis through downregulating APOE in cartilage

Osteoarthritis (OA) is a degenerative joint disease with limited effective therapies. Cold weathers have been shown to affect joint pain in OA patients. However, the impact of cold climate on OA progression is debated, with the underlying mechanisms not fully understood. To investigate the mechanisms by which low temperatures exacerbate OA, RNA sequencing on human chondrocytes cultured at 33 °C and 37 °C was performed. The gene expression in non-OA region chondrocytes and OA region chondrocytes at 33 °C was compared to that at 37 °C. The Apoe gene was identified as a temperature-relevant gene associated with exacerbation of osteoarthritis. Apoe expression was downregulated in both OA and non-OA chondrocytes cultured at 33°C compared to their 37°C counterparts. Overall design: Samples of human cartilage were taken from patients having total knee replacements. Human chondrocytes isolated from severely damaged (OA) and healthy (non-OA) regions of cartilage specimens (three patients) were cultured under two temperature conditions (37°C vs 33°C) for five days to investigate cold-associated OA progression. This experimental design generated four study groups (33°C-non-OA, 33°C-OA, 37°C-non-OA, 37°C-OA), each containing three biological replicates. The gene expression in non-OA region chondrocytes and OA region chondrocytes at 33 °C was compared to that at 37 °C