Preclinical development of a microRNA-based therapy for intervertebral disc degeneration.

Understanding the molecular mechanisms regulating the maintenance and destruction of intervertebral disc may lead to the development of new therapies for intervertebral disc degeneration (IDD). Here we present evidence from miRNA microarray analyses of clinical data sets along with in vitro and in vivo experiments that miR-141 is a key regulator of IDD. Gain- and loss-of-function studies show that miR-141 drives IDD by inducing nucleus pulposus (NP) apoptosis.

MicroRNA-218-5p as a Potential Target for the Treatment of Human Osteoarthritis.

Emerging evidence suggests that dysregulated microRNAs (miRNAs) play a pivotal role in osteoarthritis (OA), but the role of specific miRNAs remains unclear. Accordingly, we identified OA-associated miRNAs and functional validation of results. Here, we demonstrate that miR-218-5p is significantly upregulated in moderate and severe OA and correlates with scores on a modified Mankin scale.

A Small Indel Mutant Mouse Model of Epidermolytic Palmoplantar Keratoderma and Its Application to Mutant-specific shRNA Therapy.

Epidermolytic palmoplantar keratoderma (EPPK) is a relatively common autosomal-dominant skin disorder caused by mutations in the keratin 9 gene (KRT9), with few therapeutic options for the affected so far. Here, we report a knock-in transgenic mouse model that carried a small insertion-deletion (indel) mutant of Krt9, c.434delAinsGGCT (p.

Downregulation of microRNA-193a-3p is involved in invertebral disc degeneration by targeting MMP14.

Unlabelled: Accumulating evidence suggests that microRNAs (miRNAs) play an important role in intervertebral disc degeneration (IDD), but the precise role of specific miRNAs involved in this disease remains elusive. The purpose of this study was to identify IDD-specific miRNAs, followed by functional validation of results. MiRNA expression profile was determined in nucleus pulposus (NP) tissues from patients with IDD and controls, employing Solexa sequencing and quantitative real-time PCR (qRT-PCR).

Dysregulated miR-98 Contributes to Extracellular Matrix Degradation by Targeting IL-6/STAT3 Signaling Pathway in Human Intervertebral Disc Degeneration.

Intervertebral disc degeneration (IDD) is associated with dysregulated expression of microRNAs (miRNAs). However, the precise molecular mechanisms underlying this disorder remain unclear. Therefore, we tested the hypothesis that miRNAs modulate IDD through effects on the IL-6/STAT3 signaling pathway, a potential regulator of IDD.