Activation of JNK signaling in osteoblasts is inversely correlated with collagen synthesis in age-related osteoporosis

Zhang, Xin; Zhao, Gang; Ya, Zhang; Wang, Jian; Wang, Yapeng; Cheng, Long; Sun, Minxuan; Rui, Yongjun

doi:10.1016/j.bbrc.2018.08.094

Cited by 26 publications

(20 citation statements)

References 41 publications

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“…In our study, oxidoreductase activity was identi ed both by TWAS and mRNA expression pro les. Previous research shows that oxidoreductase activity was negatively related to collagen synthesis in osteoblasts [23].…”

Section: Resultsmentioning

confidence: 89%

Integrating transcriptome-wide association study and mRNA expression profile identified sensitive genes related to hand osteoarthritis

Zeng

et al. 2020

Preprint

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Background Osteoarthritis (OA) is a common skeletal system disease which proven partly related to genetic factors. The hand is a frequently affected part, which seriously affects the quality of life. But pathogenesis mechanism of hand osteoarthritis (hand OA) is still elusive. Methods The Genome-wide association study (GWAS)summary of hand OA was derived from the UK Biobank, which contains 452,264 White British individuals with 37782 osteoarthritis patients. The transcriptome-wide association study (TWAS)of hand OA was carried out using the Functional Summary-based Imputation (FUSION) using the gene expression references of muscle skeleton and blood. The significant genes identified by TWAS were further subjected to gene sets enrichment analysis (GSEA) by the Database for Annotation, Visualization and Integrated Discovery (DAVID) tool. Furthermore, we compared the identified genes and gene sets of TWAS with that of an OA mRNA expression profile to detect the genes and gene sets shared by TWAS and mRNA expression profiles of OA. Results TWAS identified 177 genes with P value < 0.05 for muscle skeleton, such as ANKRD44 (P = 0.0001), RIC3(P = 0.0003), AC005154.6 (P = 0.0004). TWAS identified 423 genes with P value < 0.05 for blood, such as CRIM1(P = 0.0002), ZNF880 (P = 0.0002), NCKIPSD (P = 0.0003).After comparing these results of TWAS to those of mRNA expression profile, we identified 5 common genes, such as DHRS3 (log2fold=-1.85, P = 3.31 × 10− 9), SKP2(log2fold = 1.36, P = 1.62 × 10− 8). GSEA of TWAS identified genes detected 51 gene ontology (GO) terms for hand OA, for example, protein binding (P = 0.0003), cytosol (P = 0.0020). We also detected 6 common GO terms shared by TWAS and mRNA expression profiling of OA, such as protein binding (PTWAS = 2.54 × 10− 4, PmRNA = 3.42 × 10− 8), extracellular exosome (PTWAS =0.02, PmRNA = 1.18 × 10− 4), cytoplasm(PTWAS =0.0183, PmRNA = 0.0048). Conclusion In this study, we selected 5 sensitive genes(DHRS3, SKP2, IRS2, TOB1, PPP1R15A)and 6 GO terms(protein binding, extracellular exosome, cytoplasm, oxidoreductase, cellular response to mechanical stimulus, oxidation-reduction process) related to the hand osteoarthritis, which may help to uncover the pathogenesis of hand osteoarthritis at the genetic and molecular levels.

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Section: Resultsmentioning

confidence: 89%

Integrating transcriptome-wide association study and mRNA expression profile identified sensitive genes related to hand osteoarthritis

Zeng

et al. 2020

Preprint

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“…The OLFM2 gene product olfactomedin 2 is an age-dependent regulator of cell differentiation and regulates axonal growth [ 36 ]. COL5A3 induces collagen synthesis and is involved in age-dependent tissue remodeling [ 37 ]. CACNA1A regulates calcium entry age-dependently and plays a role in neurodegeneration [ 38 ].…”

Section: Resultsmentioning

confidence: 99%

Telomere attrition and dysfunction: a potential trigger of the progeroid phenotype in nijmegen breakage syndrome

Habib

Kim

Neitzel

et al. 2020

Aging

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Background: Nibrin, as part of the NBN/MRE11/RAD50 complex, is mutated in Nijmegen breakage syndrome (NBS), which leads to impaired DNA damage response and lymphoid malignancy. Results: Telomere length (TL) was markedly reduced in homozygous patients (and comparably so in all chromosomes) by ~40% (qPCR) and was slightly reduced in NBS heterozygotes older than 30 years (~25% in qPCR), in accordance with the respective cancer rates. Humanized cancer-free NBS mice had normal TL. Telomere elongation was inducible by telomerase and/or alternative telomere lengthening but was associated with abnormal expression of telomeric genes involved in aging and/or cell growth. Lymphoblastoid cells from NBS patients with long survival times (>12 years) displayed the shortest telomeres and low caspase 7 activity. Conclusions: NBS is a secondary telomeropathy. The two-edged sword of telomere attrition enhances the cancer-prone situation in NBS but can also lead to a relatively stable cellular phenotype in tumor survivors. Results suggest a modular model for progeroid syndromes with abnormal expression of telomeric genes as a molecular basis. Methods: We studied TL and function in 38 homozygous individuals, 27 heterozygotes, one homozygous fetus, six NBS lymphoblastoid cell lines, and humanized NBS mice, all with the same founder NBN mutation: c.657_661del5.

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“…Within the disc structure, collagen is essential for the biomechanical stability and the overall property. Zhang et al [29] found that age was inversely correlated with collagen synthesis, suggested that with the increase of age, the decreased collagen synthesis will affect the stability of intervertebral disc structure and lead to the occurrence of related diseases such as LDH. Boos et al [30] reported that intervertebral disc degeneration is part of aging process.…”

Section: Discussionmentioning

confidence: 99%

IL1R1 Polymorphisms are Associated with Lumbar Disc Herniation Risk in the Northwestern Chinese Han Population

Zhu

Sun

et al. 2019

Med Sci Monit

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Background The aim of this study was to assess the association of single-nucleotide polymorphisms (SNPs) in IL1R1 with the risk of lumbar disc herniation (LDH) in the Han population in northwest China. Material/Methods To estimate the association of IL1R1 polymorphisms with LDH risk, Agena MassARRAY was used to determine the genotypes of 498 LDH patients and 463 controls. The association between IL1R1 variants and LDH risk was examined by logistic regression analysis with adjustments for age and gender. Stratification analysis was observed between gender and age with polymorphisms of IL1R1 . Haplotype construction and analysis in IL1R1 were also applied to detect the potential association. Results The mutant homozygous genotype in codominant model (AA versus GG, OR=2.37, 95% CI: 1.08–5.21, P =0.001) and in recessive model (AA versus GG/GA, OR=2.82, 95% CI: 1.30–6.12, P =0.005) of rs956730 were associated with an increased LDH risk in males, while rs956730 heterozygous genotype under codominant model (AG versus GG, OR=0.65, 95% CI: 0.46–0.92, P =0.001) was a protective genotype in males. In addition, the recessive model (CT/CC versus TT, OR=3.43, 95% CI: 1.11–10.57, P =0.020) of rs10490571 was associated with an increased LDH risk among people older than 50 years of age. Conclusions This study demonstrated that genetic variants in the IL1R1 genes were associated with LDH risk in the Han population of northwestern China.

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Activation of JNK signaling in osteoblasts is inversely correlated with collagen synthesis in age-related osteoporosis

Cited by 26 publications

References 41 publications

Integrating transcriptome-wide association study and mRNA expression profile identified sensitive genes related to hand osteoarthritis

Integrating transcriptome-wide association study and mRNA expression profile identified sensitive genes related to hand osteoarthritis

Telomere attrition and dysfunction: a potential trigger of the progeroid phenotype in nijmegen breakage syndrome

IL1R1 Polymorphisms are Associated with Lumbar Disc Herniation Risk in the Northwestern Chinese Han Population

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