Overexpression of Aquaporin-3 Alleviates Hyperosmolarity-Induced Nucleus Pulposus Cell Apoptosis via Regulating the ERK1/2 Pathway

Pain Res Manag. 2022 Apr 9:2022:1639560. doi: 10.1155/2022/1639560. eCollection 2022.

Abstract

Intervertebral disc degeneration (IDD) is closely related to osmolarity, which fluctuates with daily activities, and hyperosmolarity may be a contributor to nucleus pulposus (NP) cells apoptosis. Aquaporin-3 (AQP-3) belongs to the family of aquaporins and mainly transports water and other small molecular proteins, which is reduced with the aging of the intervertebral disc. ERK1/2 pathway is one type of mitogen-activated protein kinase (MAPK) and is associated with cellular apoptosis. This study was aimed to investigate the effects of AQP-3 on NP cells apoptosis induced by a hyperosmolarity and focused on the role of the ERK1/2 signaling pathway. We found that NP apoptosis could be induced by hyperosmolarity (550 mOsm/kg), and downregulation of AQP-3 and inhibition of ERK1/2 could be simultaneously observed. Therefore, lentivirus was used to enhance the expression of AQP-3 to compare apoptosis between AQP-3-overexpressed NP cells and the control NP cells. The results showed that apoptosis could be alleviated by overexpression of AQP-3 and the activity of ERK1/2 could also be promoted. Furthermore, we found that the inhibitor U0126 could partly aggravate apoptosis of the AQP-3-overexpressed NP cells. In summary, our results suggested that overexpression of AQP-3 could protect against hyperosmolarity-induced NP cell apoptosis via promoting the activity of the ERK1/2 pathway. This study may shed light on a better understanding of the pathologic mechanism of IDD and bring AQP-3 into the therapeutic approaches for IDD treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis
  • Aquaporin 3 / genetics
  • Aquaporin 3 / metabolism
  • Aquaporin 3 / pharmacology
  • Humans
  • Intervertebral Disc Degeneration*
  • MAP Kinase Signaling System
  • Nucleus Pulposus* / metabolism
  • Nucleus Pulposus* / pathology

Substances

  • Aquaporin 3