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Oestrogen and parathyroid hormone alleviate lumbar intervertebral disc degeneration in ovariectomized rats and enhance Wnt/β-catenin pathway activity.

ABSTRACT: To investigate the mitigation effect and mechanism of oestrogen and PTH on disc degeneration in rats after ovariectomy, as well as on Wnt/β-catenin pathway activity, thirty 3-month-old rats were ovariectomized and divided into three groups. Ten additional rats were used as controls. Eight weeks later, the rats were administered oestrogen or PTH for 12 weeks, and then discs were collected for tests. Results showed that nucleus pulposus cells in the Sham group were mostly notochord cells, while in the OVX group, cells gradually developed into chondrocyte-like cells. Oestrogen or PTH could partly recover the notochord cell number. After ovariectomy, the endplate roughened and endplate porosity decreased. After oestrogen or PTH treatment, the smoothness and porosity of endplate recovered. Compared with the Sham group, Aggrecan, Col2a and Wnt/β-catenin pathway expression in OVX group decreased, and either oestrogen or PTH treatment improved their expression. The biomechanical properties of intervertebral disc significantly changed after ovariectomy, and oestrogen or PTH treatment partly recovered them. Disc degeneration occurred with low oestrogen, and the underlying mechanisms involve nutrition supply disorders, cell type changes and decreased Wnt/β-catenin pathway activity. Oestrogen and PTH can retard disc degeneration in OVX rats and enhance Wnt/β-catenin pathway activity in nucleus pulposus.

SUBMITTER: Jia H

PROVIDER: S-EPMC4899752 | biostudies-other | 2016

REPOSITORIES: biostudies-other

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Project description:Accumulating evidence has indicated that noncoding RNAs are involved in intervertebral disc degeneration (IDD); however, the competing endogenous RNA (ceRNA)‑mediated regulatory mechanisms in IDD remain rarely reported. The present study aimed to comprehensively investigate the alterations in expression levels of circular RNA (circRNA), long noncoding RNA (lncRNA), microRNA (miRNA/miR) and mRNA in the nucleus pulposus (NP) of patients with IDD. In addition, crucial lncRNA/circRNA‑miRNA‑mRNA ceRNA interaction axes were screened using the GSE67567 microarray dataset obtained from the Gene Expression Omnibus database. After data preprocessing, differentially expressed circRNAs (DECs), lncRNAs (DELs), miRNAs (DEMs) or genes (DEGs) between IDD and normal controls were identified using the Linear Models for Microarray data method. A protein‑protein interaction (PPI) network was constructed for DEGs based on protein databases, followed by module analysis. The ceRNA network was constructed based on the interaction between miRNAs and mRNAs, and lncRNAs/circRNAs and miRNAs. The underlying functions of mRNAs were predicted using the Database for Annotation, Visualization and Integrated Discovery database. The present study identified 636 DECs, 115 DELs, 84 DEMs and 1,040 DEGs between patients with IDD and control individuals. PPI network analysis demonstrated that Fos proto‑oncogene, AP‑1 transcription factor subunit (FOS), mitogen‑activated protein kinase 1 (MAPK1), hypoxia inducible factor 1 subunit α (HIF1A) and transforming growth factor β1 (TGFB1) were hub genes and enriched in modules. Metastasis‑associated lung adenocarcinoma transcript 1 (MALAT1)/hsa_circRNA_102348‑hsa‑miR‑185‑5p‑TGFB1/FOS, MALAT1‑hsa‑miR‑155‑5p‑HIF1A, hsa_circRNA_102399‑hsa‑miR‑302a‑3p‑HIF1A, MALAT1‑hsa‑miR‑519d‑3p‑MAPK1 and hsa_circRNA_100086‑hsa‑miR‑509‑3p‑MAPK1 ceRNA axes were obtained by constructing the ceRNA networks. In conclusion, these identified ceRNA interaction axes may be crucial targets for the treatment of IDD.

Project description:BackgroundDisc height (DH) change is considered one of the most critical factors in assessing intervertebral disc degeneration (IVD). Pfirrmann et al. developed a scoring system for disc degeneration evaluation based on changes in DH in magnetic resonance imaging (MRI). While the relationship between DH measurements and Pfirrmann scores for disc degeneration has been explored, the validity of different DH measuring techniques or their connection with disc degeneration is yet uncertain. The present study investigates intra-rater and inter-rater agreement and reliability of different DH measurement methods on MRI and evaluates the relationship between different DH measurement methods and Pfirrmann scores of IVD degeneration, as well as between different Pfirrmann scores and clinical outcomes.MethodsAdult patients with MRI scans of the lumbar spine were recruited. Eight DH measuring techniques were tested for intra-rater and inter-rater agreement and reliability. Bland and Altman's Limits of Agreement (LOA) was used to evaluate intra-rater and inter-rater agreements. Intra-rater and inter-rater reliability were evaluated using intra-class correlations (ICC) with 95 % confidence intervals (95 % CI). The association between DH and Pfirrmann scores was examined using one-way ANOVA.ResultsExcellent intra-rater reliability was reported for 332 participants on DH (ranging from 0.912 (0.901, 0.923) to 0.973 (0.964, 0.981) and from 0.902 (0.892, 0.915) to 0.975 (0.962, 0.985) by two independent raters). All measuring methods had high intra-rater agreement, except for methods 4 and 5. All methods had good-to-excellent of inter-rater reliability on DH (ICCs ranging from 0.812 (0.795, 0.828) to 0.995 (0.994, 0.995)) except for the posterior disc material length of method 5 (ICC 0.740 (0.718, 0.761)). Methods 1 to 6 for evaluating DH in patients with spondylolisthesis had poor inter-rater reliability. The IVD levels with grades IV and V in Pfirrmann scores had significantly lower DH than the IVD levels with grades I to III in Pfirrmann scores. IVD levels with grades IV and V in Pfirrmann scores had significantly higher VAS and ODI than IVD levels with grades I in Pfirrmann scores.ConclusionA good-to-excellent intra-rater and inter-rater reliability was achieved on most DH measuring methods on MRI following a standardized and structured protocol. However, small anatomical structures and different tissue borders could influence measurements. Additionally, DH can differentiate between grade IV and V Pfirrmann scores, and severe IVD degeneration (IV and V Pfirrmann) is linked to clinical outcomes.

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Oestrogen and parathyroid hormone alleviate lumbar intervertebral disc degeneration in ovariectomized rats and enhance Wnt/β-catenin pathway activity.

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