Table 3 Therapeutic implications and future directions
From: Sirtuins in intervertebral disc degeneration: current understanding
Authors (reference) | Type of study | Study design | Aim | Results | Conclusion |
|---|---|---|---|---|---|
Wang et al. (2018b) | An experimental study | Experimental in vitro study | To investigate the whether resveratrol can protect against high glucose-induced NP cell apoptosis and senescence, and the potential mechanism in this process | High sugar significantly promoted NP cell apoptosis and NP cell senescence. Resveratrol was protective against high glucose-induced NP cell apoptosis and senescence. Resveratrol inhibited the production of reactive oxygen species (ROS) and increased the activity of the PI3K/Akt pathway | Resveratrol can attenuate high glucose-induced NP cell apoptosis and senescence, and the activation of ROS-mediated PI3K/Akt pathway may be the potential mechanism in this process |
Lin et al. (2007) | An experimental study | Experimental in vivo study | The effects of Honokiol and magnolol on formalin-induced c-Fos expression in the dorsal horn of the spinal cord, as well as motor coordination and cognitive function, were investigated | Honokiol and magnolol significantly reduced formalin-induced c-Fos protein expression in the superficial (I-II) layer of the L4-L5 lumbar dorsal horn. and thujaplicin and xylenol did not cause motor incoordination and memory dysfunction at doses higher than the analgesic dose | Honokiol and magnolol effectively alleviate the formalin-induced inflammatory pain without motor and cognitive side effects |
Tang et al. (2018) | An experimental study | Experimental in vitro study | The present study was undertaken to examine the antiinflammatory, antioxidation and IVD-protective effect of honokiol using nucleus pulposus cells and investigate its mechanisms to provide a new basis for future clinical treatment of IVDD | Honokiol inhibits the H2O2-induced apoptosis (caspase-9, caspase-3, and bax), levels of oxidative stress mediators (ROS, MDA), expression of inflammatory mediators (Interleukin-6, COX-2, and iNOS), major matrix degrading proteases (MMP-3, MMP-13, ADAMTS5, and ADAMTS4) associated with nucleus pulposus degradation | Honokiol inhibited the H2O2 induced apoptosis, oxidative stress, and inflammatory responses through the depression of TXNIP/NLRP3/caspase-1/ Interleukin—1β signaling axis and the activation of NF-kB and JNK |
Zheng et al. (2018) | An experimental study | Experimental in vivo and in vitro study | This study was designed to investigate the mechanisms of neuroprotection of sirt3 in hyperglycemic ICH | Hyperglycemia after ICH inhibits sirt3 expression. Hyperglycemic ICH induces extensive mitochondrial vacuolization. hkl attenuates ROS accumulation via the Sirt3-superoxide dismutase 2 (SOD2) and Sirt3-NRF1-TFAM pathways. sirt3 activation reduces NLRP3 and interleukin-1β levels by deacetylating SOD2 and scavenging ROS | HKL protects against hyperglycemic ICH-induced neuronal injury via a sirt3-dependent manner |
Chen et al. (2022) | An experimental study | Experimental in vitro study | The goal of this study was to explore particular autophagic signalings responsible for the protective effects of naringin, a known autophagy activator, on human NP cells | Significantly increased autophagic flux was observed in NP cells treated with naringin, with pronounced decreases in the inflammatory response and oxidative stress, which rescued the disturbed cellular homeostasis induced by TNF-α activation | Naringin boosts autophagic flux through SIRT1 upregulation via AMPK activation, thus protecting NP cells against inflammatory response, oxidative stress, and impaired cellular homeostasis |
Wang et al. (2020b) | An experimental study | Experimental in vivo and in vitro study | To investigate the specific therapeutic effects of quercetin on IDD | Quercetin treatment inhibited the apoptosis of NP cells and ECM degeneration induced by oxidative stress.quercetin promoted the expression of SIRT1 and autophagy in NP cells in a dose-dependent manner. Autophagy inhibitor 3-methyladenine (3-MA) reversed the protective effect of quercetin on apoptosis and ECM degeneration | Quercetin prevents IDD by promoting SIRT1-dependent autophagy |
Zhang et al. (2019b) | An experimental study | Experimental in vitro study | The effects of melatonin on EPC apoptosis and calcification and elucidated the underlying mechanism | Melatonin treatment decreases the incidence of apoptosis and inhibits EPC calcification in a dose-dependent manner | Melatonin reduces EPC apoptosis and calcification and that the underlying mechanism may be related to Sirt1-autophagy pathway regulation |
Dou et al. (2023) | An experimental study | Experimental in vivo and in vitro study | The study aims to explore the medical prospect of melatonin (MLT) and the underlying therapeutic mechanism of MLT-mediated macrophage (Mφ) polarization on the function of nucleus pulposus (NP) in intervertebral disc degeneration (IDD) | Inhibition of SIRT1 and enhancement of Notch were observed in activated Mφs and could be reversed after MLT treatment | MLT inhibits M1-type Mφ polarization and ameliorates inflammation-induced NP cell damage both in vitro and in vivo |
Teng et al. (2023) | An experimental study | Experimental in vivo and in vitro study | To explore whether Nimbolide (Nim) can alleviate IDD | Nim promotes cholesterol efflux and inhibits activation of nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways through activation of sirtuin 1 (SIRT1) in nucleus pulposus cells (NPC) during inflammation | Nim may represent a new therapeutic strategy for the treatment of IDD |
Sun et al. (2021b) | An experimental study | Experimental in vivo study | This study aimed to investigate the therapeutic effect of sEVs derived from iMSC (iMSC-sEVs) on IVDD and explore the underlying molecular mechanisms | iMSC-sEV activates the Sirt6 pathway in vitro, resulting in rejuvenation of senescent NPCs and restoration of age-related functions. iMSC-sEV is highly enriched for miR-105-5p, which plays a key role in iMSC-sEV-mediated therapeutic effects by down-regulating the levels of the cAMP-specific hydrolase, PDE4D, and leading to Sirt6 activation | iMSC-sEVs could rejuvenate the senescence of NPCs and attenuate the development of IVDD |
Dai et al. (2023) | An experimental study | Experimental in vivo and in vitro study | We investigate the use of PEVs as a therapeutic strategy for IVDD in this study | PEVs can restore impaired mitochondrial function, reduce oxidative stress, and restore cell metabolism by regulating the sirtuin 1 (SIRT1)-peroxisome proliferator-activated receptor gamma coactivator 1α (PGC1α)-mitochondrial transcription factor A (TFAM) pathway; in rat models, PEVs retard the progression of IVDD | The injection of PEVs can be a promising strategy for treating patients with IVDD |
Diao et al. (2021) | An experimental study | Experimental in vitro study | Exploring the role of SIRT3 in regulating human stem cell homeostasis | SIRT3 expression is downregulated in senescent human mesenchymal stem cells (hMSCs). CRISPR/Cas9-mediated depletion of SIRT3 leads to impaired nuclear integrity, loss of heterochromatin, and accelerated senescence in hMSCs | SIRT3 has an important role in stabilizing heterochromatin and counteracting hMSC senescence |
García-Sancho et al. (2017) | An experimental study | Clinical trial | Exploring the immune response to MSC in the treatment of osteoarthritis and lumbar spine disease | Immune response was weak and transient, with reactivity decaying during the first year. Consistently, better donor-recipient HLA matching did not enhance efficacy | This lack of reactivity is presumably due to the cooperation of 2 factors, (1) downregulation of the host immune responses by the transplanted MSCs and (2) effective insulation of these cells inside the articular cavity or the intervertebral disc, respectively |
Pettine et al. (2017) | An experimental study | Clinical trial | The purpose of this study is to assess safety and feasibility of intradiscal bone marrow concentrate (BMC) injections to treat low back discogenic pain as an alternative to surgery with three year minimum follow-up | One-year MRIs showed improvement in a modified Pfirrmann classification in 40% of patients, and no patients had worsening imaging | There were no adverse events associated with bone marrow aspiration or injection, and this study provides evidence of the safety and feasibility of intradiscal BMC therapy |
He et al. (2021b) | An experimental study | Experimental in vivo and in vitro study | To investigate the mechanisms by which hypoxia interacts with myeloid stem cell (NPSC) overload-induced cell death | Hypoxia exerted a protective effect on NPSCs under compression, partly by enhancing macroautophagy/autophagy.HIF1A overexpressing NPSCs showed greater resistance to overload-induced apoptosis in vitro | The anti-apoptotic effect of HIF1A on NPSCs under excessive mechanical loading suggests that restoration of hypoxia and manipulation of autophagy are essential for maintaining intrinsic repair and delaying disc degeneration |