PLCγ1 inhibition combined with inhibition of apoptosis and necroptosis increases cartilage matrix synthesis in IL‐1β‐treated rat chondrocytes
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 Cγ1 (PLCγ1), a critical...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2021-02-01
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| Series: | FEBS Open Bio |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/2211-5463.13064 |
| _version_ | 1811206024980332544 |
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| author | Xiaolei Chen Ri Chen Yang Xu Chun Xia |
| author_facet | Xiaolei Chen Ri Chen Yang Xu Chun Xia |
| author_sort | Xiaolei Chen |
| collection | DOAJ |
| description | 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 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. |
| first_indexed | 2024-04-12T03:41:33Z |
| format | Article |
| id | doaj.art-eb6fa4467b9f4207a878828a6b8f5fb8 |
| institution | Directory Open Access Journal |
| issn | 2211-5463 |
| language | English |
| last_indexed | 2024-04-12T03:41:33Z |
| publishDate | 2021-02-01 |
| publisher | Wiley |
| record_format | Article |
| series | FEBS Open Bio |
| spelling | doaj.art-eb6fa4467b9f4207a878828a6b8f5fb82022-12-22T03:49:17ZengWileyFEBS Open Bio2211-54632021-02-0111243544510.1002/2211-5463.13064PLCγ1 inhibition combined with inhibition of apoptosis and necroptosis increases cartilage matrix synthesis in IL‐1β‐treated rat chondrocytesXiaolei Chen0Ri Chen1Yang Xu2Chun Xia3Zhongshan Hospital Xiamen University ChinaSchool of Medicine Xiamen University ChinaZhongshan Hospital Xiamen University ChinaZhongshan Hospital Xiamen University ChinaOsteoarthritis (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 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.https://doi.org/10.1002/2211-5463.13064apoptosisnecroptosisosteoarthritisPLCγ1U73122 |
| spellingShingle | Xiaolei Chen Ri Chen Yang Xu Chun Xia PLCγ1 inhibition combined with inhibition of apoptosis and necroptosis increases cartilage matrix synthesis in IL‐1β‐treated rat chondrocytes FEBS Open Bio apoptosis necroptosis osteoarthritis PLCγ1 U73122 |
| title | PLCγ1 inhibition combined with inhibition of apoptosis and necroptosis increases cartilage matrix synthesis in IL‐1β‐treated rat chondrocytes |
| title_full | PLCγ1 inhibition combined with inhibition of apoptosis and necroptosis increases cartilage matrix synthesis in IL‐1β‐treated rat chondrocytes |
| title_fullStr | PLCγ1 inhibition combined with inhibition of apoptosis and necroptosis increases cartilage matrix synthesis in IL‐1β‐treated rat chondrocytes |
| title_full_unstemmed | PLCγ1 inhibition combined with inhibition of apoptosis and necroptosis increases cartilage matrix synthesis in IL‐1β‐treated rat chondrocytes |
| title_short | PLCγ1 inhibition combined with inhibition of apoptosis and necroptosis increases cartilage matrix synthesis in IL‐1β‐treated rat chondrocytes |
| title_sort | plcγ1 inhibition combined with inhibition of apoptosis and necroptosis increases cartilage matrix synthesis in il 1β treated rat chondrocytes |
| topic | apoptosis necroptosis osteoarthritis PLCγ1 U73122 |
| url | https://doi.org/10.1002/2211-5463.13064 |
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