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

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.

Oxidative Stress and Intervertebral Disc Degeneration: Pathophysiology, Signaling Pathway, and Therapy

“…Therefore, some studies began to focus on how to make stem cells withstand the damage of local oxidative stress. Studies have shown that some medicine like cyclosporine A and 1,25(OH) 2 D 3 can alleviate the apoptosis of MSC caused by oxidative stress and promote the survival of MSC [ 116 , 117 ]. At present, the abovementioned natural origin, chemical medicine, biomaterials, and stem cell therapy are still in the stage of cell and animal experiments.…”

Procyanidin B2 alleviates oxidative stress‐induced nucleus pulposus cells apoptosis through upregulating Nrf2 via PI3K–Akt pathway

“…Although numerous medicines and updated surgical techniques have been applied to solve this issue, the clinical effects remain unsatisfactory because they can only relieve symptoms without directly controlling IVDD. 26,27 Oxidative stress has been proven to participate in NPC apoptosis, which promotes the process of IVDD. 12,28 TBHP is superior to H 2 O 2 as an exogenous inducer of oxidative stress because of its high stability and slow-release capability.…”

“…The mechanisms underlying IVDD remain complicated and not fully understood. Although numerous medicines and updated surgical techniques have been applied to solve this issue, the clinical effects remain unsatisfactory because they can only relieve symptoms without directly controlling IVDD 26,27 . Oxidative stress has been proven to participate in NPC apoptosis, which promotes the process of IVDD 12,28 .…”

Researches on Stem and Progenitor Cells in Intervertebral Discs: An Analysis of the Scientific Landscape

“…Zhou XP had the most co-authorship strength (total link strength = 87), with 17 documents and 348 citations [28], followed by Liang CZ (total link strength = 85) with 16 documents and 392 citations [29] and Li FC (total link strength = 84) with 16 documents and 358 citations [30] (Figure 3(a)). Moreover, the closest collaboration organization was Shanghai Jiao Tong University (total link strength = 20) with 15 documents and 290 citations, the second organization was Yangzhou University (total link strength = 18) with 13 documents and 224 citations, and the third was Chinese Orthopaedic Regenerative Medicine Society (total link strength = 14) with 6 documents and 239 citations [31][32][33] (Figure 3(b)). Besides, the strongest collaborative country was the USA (total link strength = 58) with 94 documents and 4791 citations, followed by China (total link strength = 35) with 231 documents and 4522 citations and Japan (total link strength = 24) with 30 documents and 2612 citations (Figure 3(c)).…”