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. 2024 Jan;1870(1):166888.
doi: 10.1016/j.bbadis.2023.166888. Epub 2023 Sep 16.

Inhibition of PP2A ameliorates intervertebral disc degeneration by reducing annulus fibrosus cells apoptosis via p38/MAPK signal pathway

Pengfei Zhu  1 , Xiexing Wu  1 , Li Ni  1 , Kai Chen  2 , Zhongchen Dong  1 , Jiacheng Du  1 , Fanchen Kong  1 , Yubo Mao  1 , Huaqiang Tao  1 , Miao Chu  3 , Haiqin Mao  1 , Huilin Yang  4 , Qinbai Liu  5 , Minfeng Gan  6 , Dechun Geng  7
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Free article

Inhibition of PP2A ameliorates intervertebral disc degeneration by reducing annulus fibrosus cells apoptosis via p38/MAPK signal pathway

Pengfei Zhu et al. Biochim Biophys Acta Mol Basis Dis. 2024 Jan.
Free article

Abstract

Background: Intervertebral disc degeneration (IVDD) is considered one of the main reasons for low back pain (LBP). To date, the specific pathology of IVDD remains unclear. The annulus fibrosus (AF) is an important part of the intervertebral disc, and AF cell oxidative stress, apoptosis plays a vital role in disc degeneration. Protein phosphatase 2 A (PP2A), a serine/threonine phosphatase, has regulatory functions in various processes, including apoptosis and autophagy. However, thus far, the effect of PP2A on IVDD is not clear.

Methods: AF cells derived from caudal intervertebral discs in SD rats were used to analyze the levels of oxidative stress, apoptosis and degeneration as well as PP2A expression. A PP2A agonist (FTY720), inhibitor (microcystin-LR) and siRNA (si-PPP2CA) were employed in IVDD induced by H2O2 to investigate the levels of apoptosis and degeneration. The p38/MAPK signal pathways were evaluated, and a p38 inhibitor (SB203580) and ERK inhibitor (U0126) were added for verification. Finally, FTY720 and microcystin-LR were administered to IVDD rats to assess the effects on levels of apoptosis and degeneration and the relief of IVDD.

Results: The expression of PP2A was increased in rat AF cells after H2O2 intervention. The levels of apoptosis and degeneration were higher with upregulation of PP2A but were significantly reduced after inhibition of PP2A. The PP2A inhibitor relieved cell apoptosis and degeneration by downregulating the p38/MAPK pathway. In vivo, the knockdown of PP2A resulted in a more complete morphology of discs and less apoptotic and degenerative expression.

Conclusions: This study suggests that the downregulation of PP2 A could reduce AF cell apoptosis and degeneration via the p38/MAPK pathway. It also revealed that the inhibition of PP2 A is expected to be a therapeutic target for IVDD.

Keywords: Annulus fibrosus; Apoptosis; Intervertebral disc degeneration; MAPK pathway; Protein phosphatase 2A.

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Conflict of interest statement

Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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