Aims. Non-coding microRNA (miRNA) in extracellular vesicles (EVs) derived from mesenchymal stem cells (MSCs) may promote neuronal repair after spinal cord injury (SCI). In this paper we report on the effects of MSC-EV-microRNA-381 (miR-381) in a rodent model of SCI. Methods. In the current study, the luciferase assay confirmed a binding site of bromodomain-containing protein 4 (BRD4) and Wnt family member 5A (WNT5A). Then we detected expression of miR-381, BRD4, and WNT5A in dorsal root ganglia (DRG) cells treated with MSC-isolated EVs and measured neuron apoptosis in culture by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. A rat model of SCI was established to detect the in vivo effect of miR-381 and MSC-EVs on SCI. Results. We confirmed an interaction between miR-381 and BRD4, and showed that miR-381 overexpression inhibited the expression of BRD4 in DRG cells as well as the apoptosis of DRG cells through WNT5A via activation of Ras homologous A (RhoA)/Rho-kinase activity. Moreover, treatment of MSC-EVs rescued neuron apoptosis and promoted the recovery of SCI through inhibition of the BRD4/WNT5A axis. Conclusion. Taken altogether, miR-381 derived from MSC-EVs can promote the recovery of SCI through BRD4/WNT5A axis, providing a new perspective on SCI treatment. Cite this article: Bone Joint Res 2021;10(5):328–339

To determine whether spinal facet osteoblasts at the curve apex display a different phenotype to osteoblasts from outside the curve in patients with adolescent idiopathic scoliosis (AIS). Intrinsic differences in the phenotype of spinal facet bone tissue and in spinal osteoblasts have been implicated in the pathogenesis of AIS. However, no study has compared the phenotype of facet osteoblasts at the curve apex with the facet osteoblasts from outside the curve in patients with AIS. Facet bone tissue was collected from three sites, the concave and convex side at the curve apex and from outside the curve from three female patients with AIS (aged 13–16 years). Micro-CT analysis was used to determine the density and trabecular structure. Osteoblasts were then cultured from the sampled bone. Osteoblast phenotype was investigated by assessing cellular proliferation (MTS assay), cellular metabolism (alkaline phosphatase and Seahorse Analyser), bone nodule mineralisation (Alizarin red assay), and the mRNA expression of Wnt signalling genes (quantitative RT-PCR). Convex bone showed greater bone mineral density and trabecular thickness than did concave bone. The convex side of the curve apex exhibited a significantly higher proliferative and metabolic phenotype and a greater capacity to form mineralised bone nodules than did concave osteoblasts. mRNA expression of SKP2 was significantly greater in both concave and convex osteoblasts than in non-curve osteoblasts. The expression of SFRP1 was significantly downregulated in convex osteoblasts compared with either concave or non-curve. Intrinsic differences that affect osteoblast function are exhibited by spinal facet osteoblasts at the curve apex in patients with AIS

Introduction. Primary cilia are singular structures containing a microtubule-based axoneme which are believed to not only be mechanosensitive but also to co-ordinate many cell functions via signalling pathways including Hedgehog and Wnt. Primary cilia have previously been described on cells of mouse intervertebral discs (IVDs), but not in bovine or human IVDs. Our aim was to examine primary cilia in these species. Methods. Nucleus pulposus cells were obtained from cows with no overt disc degeneration and patients following spine surgery (for herniations and/or degenerative disc disease) and cultured until confluent before maintaining with or without serum for 24h. Primary cilia were visualised with antibodies to the axoneme (acetylated α-tubulin and Arl13b) and/or the basal body (pericentrin) using fluorescent secondary antibodies and ≥200 cells per sample were counted. Results. Primary cilia were detected in the majority of disc cells (81.2±4.1% and 54.8±28.7% with and without serum depletion, respectively, in bovine and 78.9±0.3% and 89.8±7.4% in human cells). Some cilia demonstrated abnormalities, such as bulbous tips or breaks in the axonome. Conclusion. This is the first report of primary cilia being present on human and bovine IVD cells. There remain many other aspects to be investigated, for example, their length has been shown to alter in osteoarthritic chondrocytes. If this, or the incidence of abnormalities, differs in cells from normal and abnormal discs, it could suggest new pathways of disc degeneration, as these organelles are key to so many cell functions. Conflicts of interest: None. Supported by the Orthopaedic Institute Ltd

Aims

The aim of this study was to determine the differences in spinal imaging characteristics between subjects with or without lumbar developmental spinal stenosis (DSS) in a population-based cohort.

Mesenchymal stem-cell based therapies have been proposed as novel treatments for intervertebral disc degeneration, a prevalent and disabling condition associated with back pain. The development of these treatment strategies, however, has been hindered by the incomplete understanding of the human nucleus pulposus phenotype and by an inaccurate interpretation and translation of animal to human research. This review summarises recent work characterising the nucleus pulposus phenotype in different animal models and in humans and integrates their findings with the anatomical and physiological differences between these species. Understanding this phenotype is paramount to guarantee that implanted cells restore the native functions of the intervertebral disc.

Cite this article: Bone Joint Res 2013;2:169–78.