Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

N-methyl-D-aspartate receptor together with complement C5 accelerated chondrocyte apoptosis and inflammation of osteoarthritis via mediating NLRP3

Wei Lu^1,2, Jing Yao³, Yu Cheng¹, Dongmei Mao³, Di Luo², Lin Wang³

¹School of Anesthesia, Guizhou Medical University, 4 Beijing Road, Guiyang, Guizhou, China; ²Guizhou Cancer Hospital, No. 1 Beijing West Road, Guiyang, Guizhou, China; ³Department of Pain, Affiliated Hospital of Guizhou Medical University, 4 Beijing Road, Guiyang, Guizhou, China.

For correspondence:- Lin Wang Email: jbv8566@126.com

Accepted: 30 March 2023 Published: 29 April 2023

Citation: Lu W, Yao J, Cheng Y, Mao D, Luo D, Wang L. N-methyl-D-aspartate receptor together with complement C5 accelerated chondrocyte apoptosis and inflammation of osteoarthritis via mediating NLRP3. Trop J Pharm Res 2023; 22(4):759-766 doi: 10.4314/tjpr.v22i4.7

© 2023 The authors.
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Abstract

Purpose: NMDAR and complements have been reported to facilitate progression of OA but the correlation between NMDAR and complement C5 in OA is unknown. Therefore, NMDAR antagonist, MK801 and C5 inhibitor, eculizumab were applied to measure functions of NMDAR and C5 in SW1353 cells.

Methods: SW1353 cells were first induced with LPS (5 μg/ml and 10 μg/ml) and later 10 μg/ml LPS induced SW1353 cells were treated by MK801 (100 μM) and eculizumab (100μg/ml). Thereafter, NR1, NR2A and C5 RNA expressions were assessed by RT-qPCR in LPS induced SW1353 cells and NR1 with NR2A was measured under MK801 treatment while C5 was analyzed by eculizumab treatment. Later, apoptosis of SW1353 cells were examined through flow cytometry. Inflammatory cytokines TNF-α, IL-6 and NLRP3 RNA expressions were evaluated by RT-qPCR in SW1353 cells from different groups.

Results: NR1, NR2A and C5 RNA expressions were all significantly upregulated after LPS induction with upregulated apoptosis and increased TNF-α, IL-6 and NLRP3. Treatment of MK801, a NMDAR antagonist, reduced NR1 and NR2A levels. Moreover, apoptosis rate of SW1353 and RNA expressions of inflammatory cytokines were all markedly reduced with MK801. Further, eculizumab treatment significantly downregulated C5 RNA expression in LPS induced SW1353 cells. Added eculizumab also enhanced functions of MK801 in repressing apoptosis rate and inflammatory factors RNA expressions.

Conclusion: MK801 and eculizumab suppressed apoptosis and inflammatory response in SW1353 cells through inhibiting NMDAR and complement C5.

Keywords: NMDAR, complement C5, NLRP3, osteoarthritis