PDLIM2 protects articular chondrocytes from lipopolysaccharide-induced apoptosis, degeneration and inflammatory injury through down-regulation of nuclear factor (NF)-κB signaling.

Qinyue Guo, Jing Xu, Qindong Shi, Shufang Wu

International immunopharmacology 2020 Nov

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Excessive inflammatory response-induced apoptosis and the degeneration of articular chondrocytes contribute to the development and progression of osteoarthritis. PDZ and LIM domain containing protein 2 (PDLIM2) has emerged as one of the pivotal regulators in orchestrating an inflammatory response through regulating the activity of transcription factor nuclear factor (NF)-κB. However, whether PDLIM2 participates in the articular chondrocyte-associated inflammatory response in osteoarthritis remains unknown. In the current study, we aimed to explore the biological function of PDLIM2 in lipopolysaccharide (LPS)-stimulated articular chondrocytes, an in vitro model of osteoarthritis. Herein, we found that PDLIM2 expression was significantly down-regulated in chondrocytes in response to LPS exposure. Functional experiments revealed that PDLIM2 overexpression increased the viability and decreased the apoptosis of chondrocytes following LPS treatment. Moreover, PDLIM2 overexpression attenuated LPS-induced degeneration of chondrocytes via the down-regulation of matrix metalloproteinase (MMP)-3 and MMP-13 and the up-regulation of COL2A1 and ACAN. In addition, the overexpression of PDLIM2 decreased LPS-induced production of interleukin (IL)-1β, IL-6 and TNF-α. In contrast, depletion of PDLIM2 exhibited the opposite effect. Mechanism research elucidated that PDLIM2 repressed the activation of NF-κB signaling associated with the down-regulation of NF-κB p65 protein expression. PDLIM2 depletion-exacerbated LPS-induced injury was significantly reversed by NF-κB inhibition. Taken together, these results demonstrate that PDLIM2 overexpression attenuates LPS-induced injury of articular chondrocytes through the inactivation of NF-κB signaling. Copyright © 2020 Elsevier B.V. All rights reserved.

Citation

Qinyue Guo, Jing Xu, Qindong Shi, Shufang Wu. PDLIM2 protects articular chondrocytes from lipopolysaccharide-induced apoptosis, degeneration and inflammatory injury through down-regulation of nuclear factor (NF)-κB signaling. International immunopharmacology. 2020 Nov;88:106883