PLCγ1 inhibition combined with inhibition of apoptosis and necroptosis increases cartilage matrix synthesis in IL-1β-treated rat chondrocytes
- PMID: 33326693
- PMCID: "VSports" PMC7876495
- DOI: 10.1002/2211-5463.13064
PLCγ1 inhibition combined with inhibition of apoptosis and necroptosis increases cartilage matrix synthesis in IL-1β-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 VSports手机版. New, disease-modifying therapies are needed. A potential novel molecular target is phospholipase Cγ1 (PLCγ1), a critical enzyme with important functions including calcium signaling regulation and cell proliferation. In rat chondrocytes treated with IL-1β (20 ng·mL-1 for 36 h), inhibition of PLCγ1 with U73122 (2 μm for 12 h) increased levels and expression of the cartilage matrix components Collagen2 and Aggrecan. This beneficial effect of PLCγ1 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-1β + U73122-treated chondrocytes with inhibitors of apoptosis (Z-VAD, 10 μm) and necroptosis (Nec-1, 30 μm) 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 PLCγ1 inhibition may be a viable approach for an OA therapy, if combined with targeted inhibition of chondrocyte apoptosis and necroptosis. .
Keywords: PLCγ1; U73122; apoptosis; necroptosis; osteoarthritis. V体育安卓版.
© 2020 The Authors. FEBS Open Bio published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies V体育ios版. .
Conflict of interest statement
The authors declare no conflict of interest.
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