PLC?1 inhibition combined with inhibition of apoptosis and necroptosis increases cartilage matrix synthesis in IL-1?-treated rat chondrocytes.

ABSTRACT: Osteoarthritis (OA) is an age-related, chronic degenerative disease. With the increasing median age of the population, this disease has become an important public health problem. New, disease-modifying therapies are needed. A potential novel molecular target is phospholipase C?1 (PLC?1), a critical enzyme with important functions including calcium signaling regulation and cell proliferation. In rat chondrocytes treated with IL-1? (20 ng·mL^-1 for 36 h), inhibition of PLC?1 with U73122 (2 ?m for 12 h) increased levels and expression of the cartilage matrix components Collagen2 and Aggrecan. This beneficial effect of PLC?1 inhibition was counteracted by increased chondrocyte apoptosis and necroptosis, increased cell death, and increase levels of ROS, all potentially negative for OA. Combined treatment of IL-1? + U73122-treated chondrocytes with inhibitors of apoptosis (Z-VAD, 10 ?m) and necroptosis (Nec-1, 30 ?m) enhanced the increases in levels and expression of Collagen2 and Aggrecan, and prevented the increases in cell death and ROS levels. These results suggest that PLC?1 inhibition may be a viable approach for an OA therapy, if combined with targeted inhibition of chondrocyte apoptosis and necroptosis.

SUBMITTER: Chen X 

PROVIDER: S-EPMC7876495 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature