1. Academic Validation
  2. 1,25(OH)2D3 Mitigates Oxidative Stress-Induced Damage to Nucleus Pulposus-Derived Mesenchymal Stem Cells through PI3K/Akt Pathway

1,25(OH)2D3 Mitigates Oxidative Stress-Induced Damage to Nucleus Pulposus-Derived Mesenchymal Stem Cells through PI3K/Akt Pathway

  • Oxid Med Cell Longev. 2022 Mar 18;2022:1427110. doi: 10.1155/2022/1427110.
Jun-Wu Wang 1 Lei Zhu 1 Peng-Zhi Shi 2 Ping-Chuan Wang 1 Yan Dai 3 Yong-Xiang Wang 1 Xu-Hua Lu 4 Xiao-Fei Cheng 5 Xin-Min Feng 1 Liang Zhang 1
Affiliations

Affiliations

  • 1 Department of Orthopedics, Clinical Medical College of Yangzhou University, Yangzhou 225001, China.
  • 2 Graduate School of Dalian Medical University, Dalian 116000, China.
  • 3 Medical Experimental Research Center, Clinical Medical College of Yangzhou University, Yangzhou 225001, China.
  • 4 Department of Orthopedics, Changzheng Hospital of The Second Military Medical University, Shanghai 200003, China.
  • 5 Department of Orthopedic Surgery, Shanghai Key Laboratory of Orthopedics Implants, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200011, China.
Abstract

Intervertebral disc degeneration (IVDD) is one of the main causes of low back pain. The local environment of the degenerated intervertebral disc (IVD) increases oxidative stress and Apoptosis of endogenous nucleus pulposus-derived mesenchymal stem cells (NPMSCs) and weakens its ability of endogenous repair ability in degenerated IVDs. A suitable concentration of 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3) has been certified to reduce oxidative stress and cell Apoptosis. The current study investigated the protective effect and potential mechanism of 1,25(OH)2D3 against oxidative stress-induced damage to NPMSCs. The present results showed that 1,25(OH)2D3 showed a significant protective effect on NPMSCs at a concentration of 10-10 M for 24 h. Protective effects of 1,25(OH)2D3 were also exhibited against H2O2-induced NPMSC senescence, mitochondrial dysfunction, and reduced mitochondrial membrane potential. The Annexin V/PI Apoptosis detection assay, TUNEL assay, immunofluorescence, western blot, and real-time quantitative polymerase chain reaction assay showed that pretreatment with 1,25(OH)2D3 could alleviate H2O2-induced NPMSC Apoptosis, including the Apoptosis rate and the expression of proapoptotic-related (Caspase-3 and Bax) and antiapoptotic-related (Bcl-2) proteins. The intracellular expression of p-Akt increased after pretreatment with 1,25(OH)2D3. However, these protective effects of 1,25(OH)2D3 were significantly decreased after the PI3K/Akt pathway was inhibited by the LY294002 treatment. In vivo, X-ray, MRI, and histological analyses showed that 1,25(OH)2D3 treatment relieved the degree of IVDD in Sprague-Dawley rat disc puncture models. In summary, 1,25(OH)2D3 efficiently attenuated oxidative stress-induced NPMSC Apoptosis and mitochondrial dysfunction via PI3K/Akt pathway and is a promising candidate treatment for the repair of IVDD.

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