The roles and perspectives of microRNAs as biomarkers for intervertebral disc degeneration

Zhou, Xin; Chen, Lili; Grad, Sibylle; Alini, Mauro; Pan, Haobo; Yang, Dazhi; Zhen, Wu; Li, Zhizhong; Huang, Shishu; Peng, Songlin

doi:10.1002/term.2261

Cited by 47 publications

(52 citation statements)

References 87 publications

(100 reference statements)

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“…In addition, no studies were found that studied molecular biomarkers in relation to progression of DD. This is surprising, as biomarkers are subject of many studies in relation to DD, but are presumably related to the onset of DD and not progression, which is beyond the scope of this review. Second, there was a high heterogeneity between studies regarding the definition of DD and its progression, which made it impossible to pool data.…”

Section: Discussionmentioning

confidence: 95%

Prognostic factors in the progression of intervertebral disc degeneration: Which patient should be targeted with regenerative therapies?

et al. 2019

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Objective Possible regenerative treatments for lumbar intervertebral disc degeneration (DD) are rapidly emerging. There is consensus that the patient that would benefit most has early‐stage DD, with a predicted deterioration in the near future. To identify this patient, the aim of this study was to identify prognostic factors for progression of DD. Study design Systematic review. Methods A systematic search was performed on studies evaluating one or more prognostic factor(s) in the progression of DD. The criteria for inclusion were (a) patients diagnosed with DD on MRI, (b) progression of DD at follow‐up, and (c) reporting of one or more prognostic factor(s) in progression of DD. Two authors independently assessed the methodological quality of the included studies. Due to heterogeneity in DD determinants and outcomes, only a best‐evidence synthesis could be conducted. Results The search generated 3165 references, of which 16 studies met our inclusion criteria, involving 2.423 patients. Within these, a total of 23 clinical and environmental and 12 imaging factors were identified. There was strong evidence that disc herniation at baseline is associated with progression of DD at follow‐up. There is limited evidence that IL6 rs1800795 genotype G/C male was associated with no progression of DD. Some clinical or environmental factors such as BMI, occupation and smoking were not associated with progression. Conclusions Disc herniation is strongly associated with the progression of DD. Surprisingly, there was strong evidence that smoking, occupation, and several other factors were not associated with the progression of DD. Only one genetic variant may have a protective effect on progression, otherwise there was conflicting or only limited evidence for most prognostic factors. Future research into these prognostic factors with conflicting and limited evidence is not only needed to determine which patients should be targeted by regenerative therapies, but will also contribute to spinal phenotyping.

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Section: Discussionmentioning

confidence: 95%

Prognostic factors in the progression of intervertebral disc degeneration: Which patient should be targeted with regenerative therapies?

et al. 2019

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“…Firstly, GPC6 expressed in chondrocytes of mouse growth plates, and might induce the degeneration of cartilage endplates and even structural abnormal ossification by WNT and hedgehog signaling pathways. (Campos‐Xavier et al, ; Daly et al, ; Zhou et al, ). Secondly, GPC6 may affect the main components of the nucleus pulposus (NP) by BMP‐7, such as type I and type II collagen (Kim et al, ).…”

Section: Discussionmentioning

confidence: 99%

“…Especially, GPC6 may be associated with LDH by causing osteoporosis (Dequeker, 1997;Im & Kim, 2014) as well as play an important role in cartilage damage by WNT pathway, whose structures are a main part of the endplate (van den Bosch et al, 2015;Daly, Ghosh, Jenkin, Oehme, & Goldschlager, 2016). In addition, GPC6 is also reported to be responsible for LDD by changing the internal environment of nucleus pulposus (NP) cells (Zhou et al, 2017). Thus, we highlighted the importance of GPC6 in the development of LDH, and speculated that single-nucleotide polymorphisms (SNPs) of GPC6 are involved in LDH occurrence.…”

Section: Introductionmentioning

confidence: 99%

Association of glypican‐6 polymorphisms with lumbar disk herniation risk in the Han Chinese population

et al. 2019

Molec Gen & Gen Med

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Background Lumbar disk herniation (LDH) is a degenerative disorder, which partly results from complex genetic factors. The aim of the study was to investigate the potential associations between glypican‐6 ( GPC6 ) variants and LDH risk in Han Chinese population. Methods A total of 508 Han Chinese LDH patients and 508 healthy controls were recruited in this study. Six single‐nucleotide polymorphisms (SNPs) in GPC6 were selected and genotyped using an Agena MassARRAY platform. We used logistic regression method to evaluate the linkage between GPC6 variants and LDH risk by calculating the odds ratio (OR) and 95% confidence intervals (CIs) in multiple genetic models. HaploReg database was used for SNP functional annotation. Results Our result revealed GPC6 rs4773724 was associated with a decreased risk of LDH in allele model (OR = 0.82, 95% CI: 0.68–0.98, p = 0.026), whereas rs1008993 increased the LDH risk (OR = 1.34, 95% CI: 1.05–1.71, p = 0.020). Besides, we also found rs4773724 and rs9523981 were associated with susceptibility of LDH among individuals whose age are less than 45. And rs1008993 was associated with increased LDH risk in males. Furthermore, Haplotype analysis showed that the TT (rs4773724, rs1008993) haplotype and GC (rs4773724, rs1008993) haplotype had the opposite effects on the susceptibility of LDH. Conclusions For the first time, we suggest that rs4773724 and rs1008993 in GPC6 were considered as a protective factor and a risk factor for LDH in Han Chinese population, respectively. These results provide new ideas for the treatment and prevention of LDH in Han Chinese population.

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“…184 Notably, expression profiling studies have identified a number of dysregulated miRNAs in human degenerated IVDs when compared to control specimens. 185–188 Another study reported higher levels of miR-100 in human lumbar degenerated discs compared to traumatized, non-degenerated human specimens and that altered expression levels correlated with FGFR1. 189 A polymorphism in pre-miR-125a (Rs12976445) has been shown to result in a significant reduction in the amount of mature miR-125a by compromising its processing, thereby leading to less efficient inhibition of target genes.…”

Section: Mirnas Associated With Skeletal Disease and Other Orthopaedimentioning

confidence: 99%

MicroRNAs in orthopaedic research: Disease associations, potential therapeutic applications, and perspectives

McAlinden

2017

Journal Orthopaedic Research

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MicroRNAs (miRNAs) are small non-coding RNAs that function to control many cellular processes by their ability to suppress expression of specific target genes. Tens to hundreds of target genes may be affected by one miRNA, thereby resulting in modulation of multiple pathways in any given cell type. Therefore, altered expression of miRNAs (i.e., during tissue development or in scenarios of disease or cellular stress) can have a profound impact on processes regulating cell differentiation, metabolism, proliferation, or apoptosis, for example. Over the past 5-10 years, thousands of reports have been published on miRNAs in cartilage and bone biology or disease, thus highlighting the significance of these non-coding RNAs in regulating skeletal development and homeostasis. For the purpose of this review, we will focus on miRNAs or miRNA families that have demonstrated function in vivo within the context of cartilage, bone or other orthopaedicrelated tissues (excluding muscle). Specifically, we will discuss studies that have utilized miRNA transgenic mouse models or in vivo approaches to target a miRNA with the aim of altering conditions such as osteoarthritis, osteoporosis and bone fractures in rodents. We will not discuss miRNAs in the context skeletal cancers since this topic is worthy of a review of its own. Overall, we aim to provide a comprehensive description of where the field currently stands with respect to the therapeutic potential of specific miRNAs to treat orthopaedic conditions and current technologies to target and modify miRNA function in vivo. KeywordsMicroRNAs (miRNAs); cartilage; bone; skeletal development; osteoarthritis MicroRNA (miRNAs) are small non-coding RNA molecules (typically 19-24 nucleotides in length) that function in RNA silencing and post-transcriptional regulation (suppression) of gene expression. 1 While the majority of miRNAs are located within the cell, some miRNAs, commonly known as circulating miRNA or extracellular miRNA, have also been detected outside the cell in the extracellular matrix, in various biological fluids, or in cell culture. HHS Public Access Author Manuscript Author ManuscriptAuthor ManuscriptAuthor Manuscript miRNAs were first discovered over 20 years ago in the nematode Caenorhabditis elegans with the identification of the developmental regulator lin-4. 3 Since then, thousands of miRNAs have been identified and investigated, with a wide distribution in animals, plants, and viruses. 4 MicroRNAs are ubiquitously expressed in different organisms, and many of them are phylogenetically conserved. 5 To date, over 28,000 miR-NAs from various species are listed in the miRBase website (http://www.mirbase.org). Specifically, 2,588 mature miRNAs have been identified in humans and 1,915 mature miRNAs have been reported in mice.With respect to miRNA biosynthesis, transcription of miRNA genes that are located either intergenically or intragenically is mediated primarily by RNA polymerase II in eukaryotes, although RNA polymerase III has also been shown to transcrib...

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The roles and perspectives of microRNAs as biomarkers for intervertebral disc degeneration

Cited by 47 publications

References 87 publications

Prognostic factors in the progression of intervertebral disc degeneration: Which patient should be targeted with regenerative therapies?

Prognostic factors in the progression of intervertebral disc degeneration: Which patient should be targeted with regenerative therapies?

Association of glypican‐6 polymorphisms with lumbar disk herniation risk in the Han Chinese population

MicroRNAs in orthopaedic research: Disease associations, potential therapeutic applications, and perspectives

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