Risk Factor For Intervertebral Disc Degeneration Research Articles

Causal effects of skin microbiota on intervertebral disk degeneration, low back pain and sciatica: a two-sample Mendelian randomization study

ObjectiveThe purpose of this study is to use two-sample Mendelian randomization (MR) to investigate the causal relationship between skin microbiota, especially Propionibacterium acnes, and intervertebral disc degeneration (IVDD), low back pain (LBP) and sciatica.MethodsWe conducted a two-sample MR using the aggregated data from the whole genome-wide association studies (GWAS). 150 skin microbiota were derived from the GWAS catalog and IVDD, LBP and sciatica were obtained from the IEU Open GWAS project. Inverse-variance weighted (IVW) was the primary research method, with MR-Egger and Weighted median as supplementary methods. Perform sensitivity analysis and reverse MR analysis on all MR results and use multivariate MR to adjust for confounding factors.ResultsMR revealed five skin microbiota associated with IVDD, four associated with LBP, and two with sciatica. Specifically, P.acnes in sebaceous skin environments were associated with reduced risk of IVDD; IVDD was found to increase the abundance of P.acnes in moist skin. Furthermore, ASV010 [Staphylococcus (unc.)] from dry skin was a risk factor for LBP and sciatica; ASV045 [Acinetobacter (unc.)] from dry skin and Genus Rothia from dry skin exhibited potential protective effects against LBP; ASV065 [Finegoldia (unc.)] from dry skin was a protective factor for IVDD and LBP. ASV054 [Enhydrobacter (unc.)] from moist skin, Genus Bacteroides from dry skin and Genus Kocuria from dry skin were identified as being associated with an increased risk of IVDD. Genus Streptococcus from moist skin was considered to be associated with an increased risk of sciatica.ConclusionsThis study identified a potential causal relationship between skin microbiota and IVDD, LBP, and sciatica. No evidence suggests skin-derived P.acnes is a risk factor for IVDD, LBP and sciatica. At the same time, IVDD can potentially cause an increase in P.acnes abundance, which supports the contamination theory.

MicroRNA-155 suppressed cholesterol-induced matrix degradation, pyroptosis and apoptosis by targeting RORα in nucleus pulposus cells

Intervertebral disc degeneration (IDD) is associated with low back pain, yet its inherent mechanism remains obscure. Hypercholesteremia was regarded as a risk factor for IDD, and our previous study showed that cholesterol accumulation could elicit matrix degradation in the nucleus pulposus (NP). MicroRNA-155 (miR-155) was substantiated as protective in IDD, but its role in cholesterol-induced IDD was unclear. The present study investigated whether miR-155 could mediate cholesterol-related IDD and its internal mechanisms. In vivo experiments revealed high-fat diet-induced hypercholesteremia in wild-type (WT) mice along with the occurrence of IDD, whereas Rm155LG transgenic mice showed milder NP degeneration, as evidenced by Saffron O-fast green (SF) staining and immunohistochemistry (IHC). Meanwhile, IHC showed that NLRP3 and Bax expression was also suppressed in Rm155LG mice. In vitro studies using Western blotting (WB) and immunofluorescence (IF) confirmed that the miR-155 mimic could alleviate cholesterol-induced matrix degradation, apoptosis and pyroptosis in NP. Moreover, RORα was upregulated in severely degenerated NP compared to mild IDD. It was also noted that RORα was suppressed in Rm155LG mice. In this study, we demonstrated that miR-155 could target RORα and that inhibition of RORα could prevent cholesterol-induced matrix degradation, apoptosis, and pyroptosis in NP, indicating the protective effect of miR-155 in cholesterol-induced IDD by targeting RORα.

Effects of Caffeine on Intervertebral Disc Cell Viability in a Whole Organ Culture Model.

Study Design:Controlled laboratory study.Objective:To investigate the impact of exposure to physiologically relevant caffeine concentrations on intervertebral disc (IVD) cell viability and extracellular matrix composition (ECM) in a whole organ culture model as potential contributing mechanisms in development and progression of IVD disorders in humans. Primary outcome measures were IVD viable cell density (VCD) and ECM composition.Methods:A total of 190 IVD whole organ explants from tails of 16 skeletally mature rats—consisting of cranial body half, endplate, IVD, endplate, and caudal body half—were harvested. IVD explants were randomly assigned to 1 of 2 groups: uninjured (n = 90) or injured (20G needle disc puncture/aspiration method, n = 100). Explants from each group were randomly assigned to 1 of 3 treatment groups: low caffeine (LCAF: 5 mg/L), moderate caffeine (MCAF: 10 mg/L), and high caffeine (HCAF: 15 mg/L) concentrations.Results:Cell viability was significantly higher in the low-caffeine group compared with the high-caffeine group at day 7 (P = .037) and in the low-caffeine group compared with the medium- and high-caffeine groups at day 21 (P ≤ .004). Analysis of ECM showed that all uninjured and control groups had significantly higher (P < .05) glycosaminoglycan concentrations compared with all injured groups. Furthermore, we observed a temporal, downward trend in proteoglycan to collagen ratio for the caffeine groups.Conclusions:Caffeine intake may be a risk factor for IVD degeneration, especially in conjunction with disc injury. Mechanisms for caffeine associated disc degeneration may involve cell and ECM, and further studies should elucidate mechanistic pathways and potential benefits for caffeine restriction.

The Sirt1/P53 Axis in Diabetic Intervertebral Disc Degeneration Pathogenesis and Therapeutics.

Intervertebral disc degeneration (IDD) is one of the major causes of low back pain. Diabetes is a risk factor for IDD and may aggravate IDD in rats; however, the mechanism is poorly understood. Previously, we demonstrated that apoptosis and senescence were increased in diabetic nucleus pulposus (NP) tissues; in the current study, we found that hyperglycaemia may promote the incidence of apoptosis and senescence in NP cells in vitro. Meanwhile, the acetylation of P53, a master transcription factor of apoptosis and senescence, was also found increased in diabetic NP tissues in vivo as well as in hyperglycaemic NP cells in vitro. Sirt1 is an NAD+-dependent deacetylase, and we showed that the expression of Sirt1 was decreased in NP tissues, while hyperglycaemia could suppress the expression and activity of Sirt1 in NP cells. Furthermore, we demonstrated that butein may inhibit acetylation of P53 and protect NP cells against hyperglycaemia-induced apoptosis and senescence through Sirt1 activation, as the Sirt1 inhibitor Ex527 may counteract the protective effect of butein in hyperglycaemic NP cells. An in vivo study showed that butein could ameliorate the IDD process in diabetic rats, while Sirt1 was increased and acetyl-p53 was decreased in NP tissues in butein-treated rats. These results indicate that the Sirt1/P53 axis is involved in the pathogenesis of diabetic IDD and may serve as a therapeutic target for diabetic IDD.

Deletion of Opg Leads to Increased Neovascularization and Expression of Inflammatory Cytokines in the Lumbar Intervertebral Disc of Mice.

Neovascularization and expression of inflammatory cytokines were examined in Osteoprotegerin (Opg) knockout (KO) mice that show intervertebral disc (IVD) degeneration. The aim of this study was to clarify the pathological changes in lumbar IVD degeneration in Opg KO mice. Osteoporosis is a controversial risk factor for IVD degeneration. Deletion of Opg resulted in IVD degeneration in mice. Neovascularization and inflammatory cytokines are key factors in IVD degeneration. Opg KO mice and their wild-type (WT) littermates were euthanized. Lumbar IVDs were harvested. Safranin O/Fast Green staining was performed to examine the pathological changes. Microcomputed tomographic (micro-CT) analysis was performed to determine the structural changes at the junction of lumbar IVD cartilage and vertebrae. Tartrate-resistant acid phosphatase (TRAP) staining was performed to evaluate osteoclast formation. Protein expression of vascular endothelial growth factor A (VEGF-A), CD31, VE-cadherin, CD 34, interleukin-1β (IL-1β), and tumor necrosis factors α (TNF-α) were analyzed by immunohistochemistry (IHC) assays. Gene expressions of IL-1β, IL-6, and TNF-α were analyzed by real-time polymerase chain reaction (RT-PCR). In 12-week-old Opg KO mice, new bone was formed in the endplate cartilage of lumbar IVDs and this became more obvious in 24-week-old Opg KO mice. Three-dimensional (3D) μCT reconstruction analyses showed that the edges of the L4 and L5 vertebrae were rugged with bone marrow cavities in it. Protein expression of VEGF-A, CD31, VE-cadherin, and CD34 was increased in the endplate and growth plate of lumbar IVDs of Opg KO mice. Gene expression of IL-1β, IL-6, and TNF-α as well as protein expression of IL-1β and TNF-α were highly expressed in the lumbar IVDs of Opg KO mice. Deletion of Opg leads to increased neovascularization and expression of inflammatory cytokines in the lumbar disc in Opg KO mice, which may play important roles in IVD degeneration. N/A.