Background. In vivo evaluation of IVD strains is crucial to better understand normal and pathological IVD mechanics, and to evaluate the effectiveness of treatments. This study aimed to 1) develop a novel in vivo technique based on 3T MRI and digital volume correlation (DVC) to measure strains within IVDs and 2) to use this technique to resolve 3D strains within IVDs of healthy volunteers during extension. Methods. This study included 40 lumbar IVDs from eight healthy subjects. The optimal MR sequence to minimise DVC uncertainties was identified by scanning one subject with four different sequences: CISS, T1VIBE, T2SPACE, and T2TSE. To assess the repeatability of the strain measurements in spines with different anatomical and morphological variations four subjects were scanned with the optimal sequence, and uncertainties of the strain measurements were quantified. Additionally, to calculate 3D strains during extension, MRIs were acquired from six subjects in both the neutral position and after full extension. Results. Measurement errors were lowest when using the T2TSE sequence (precision=0.33 ± 0.10%, accuracy=0.48 ± 0.11%). The largest average maximum tensile and shear strains were seen at the L2-L3 level in all volunteers (7.2 ± 1.5% and 6.8 ± 1.1%, respectively), while the L5-S1 level experienced the lowest average tensile and shear strains (3.5 ± 1.0% and 3.9 ± 0.7%, respectively). Conclusion. The findings of this study establish clinical MRI-based DVC (MRI-DVC) as a new tool for in vivo strain measurement within human IVDs. MRI-DVC successfully provided internal strain distributions within IVDs and has great potential to be used for a wide range of clinical applications. Conflict of interest: No conflicts of interest. Source of funding: This work was supported by the EPSRC, New Investigator Award, EP/V029452/1

Aims

In this investigation, we administered oxidative stress to nucleus pulposus cells (NPCs), recognized DNA-damage-inducible transcript 4 (DDIT4) as a component in intervertebral disc degeneration (IVDD), and devised a hydrogel capable of conveying small interfering RNA (siRNA) to IVDD.

Introduction. Adolescent idiopathic scoliosis (AIS) is the most common spinal deformity in children, and its cause is unknown. Recently, researchers have traced a defect in the gene CHD7 to AIS. CHD7 encodes for a chromodomain helicase of the DNA-binding domain protein family and is thought to have a crucial role in many basic cellular functions. However, the functional role of CHD7 in AIS is still elusive. In this study, we investigated the potential pathogenic effect of gene defects in CHD7 in vivo by evaluating their effect on spine formation and development in zebrafish. Methods. To investigate the function of the CHD7 encoded protein, we generated an antisense morpholino oligonucleotide against the CHD7 gene to disrupt the translation of the gene transcripts and knockdown the levels of its protein. The morpholino was injected into single-cell stage zebrafish embryos. The injected fish were allowed to develop and were then assessed for distinct phenotypes reminiscent of scoliosis by histological stains. Results. Knockdown of CHD7 resulted in a spectrum of ocular and heart anomalies. We noted that 26% of the zebrafish morphants exhibited curvature of the body axis at early stages. Histological stains of the vertebrae at later stages revealed that the spine of the zebrafish morphant had abnormal kinks rather than scoliotic curves. These defects were accompanied by reduced vertebral mineralisation around the kink area. The CHD7 morphant also showed severe cranial nerve abnormalities and had missing or malformed otolith—a part of the vestibular system analogous to the human ear. Conclusions. Our findings indicate a key role of CHD7 in eye, heart, and ear development but not in the onset of skeletal deformities as observed in scoliosis. Our results are similar to the congenital abnormities associated with CHD7 mutations in the CHARGE syndrome. Acknowledgments. This study is supported by the Yves Cotrel Fondation