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3D assessment of intervertebral disc degeneration in zebrafish identifies changes in bone density that prime disc disease

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Bone Research 2021年第4期9卷 521-536页

作者： Erika Kague Francesco Turci elis newman Yushi Yang Kate Robson Brown Mona S.Aglan Ghada A.Otaify Sarnia A.Temtamy Victor L.Ruiz-Perez Stephen Cross C.Patrick Royall P.Eckhard Witten Chrissy L.Hammond School of Physiology Pharmacology and NeuroscienceBiomedical SciencesUniversity of BristolBristolUK School of Physics HH Wills Physics LaboratoryUniversity of BristolBristolUK Centre for Nanoscience and Quantum Information University of BristolBristolUK Bristol Centre for Functional Nanomaterials University of BristolBristolUK Department of Anthropology and Archaeology University of BristolBristolUK Department of Mechanical Engineering University of BristolBristolUK Clinical Genetics Department Human Genetics and Genome Research DivisionCenter of Excellence for Human GeneticsNational Research CentreCairoEgypt lnstituto de Investigaciones Biomedicas de Madridand Ciber de Enfermedades Raras(CIBERER)MadridSpain Wolfson Bioimaging Facility Biomedical SciencesUniversity of BristolBristolUK School of Chemistry University of BristolBristolUK Evolutionary Developmental Biology Department of BiologyGhent UniversityGhentBelgium

Back pain is a common condition with a high social impact and represents a global health *** disc disease(IVDD)is one of the major causes of back pain;no therapeutics are currently available to reverse this *** impact of bone mineral density(BMD)on IVDD has been controversial,with some studies suggesting osteoporosis as causative for IVDD and others suggesting it as protective for *** studies to evaluate the influence of genetic components of BMD in IVDD could highlight opportunities for drug development and *** taking a holistic 3D approach,we established an aging zebrafish model for spontaneous *** BMD in aging,detected by automated computational analysis,is caused by bone deformities at the ***,aged zebrafish spines showed changes in bone morphology,microstructure,mineral heterogeneity,and increased fragility that resembled *** of the discs recapitulated IVDD symptoms found in humans:the intervertebral ligament(equivalent to the annulus fibrosus)showed disorganized collagen fibers and herniation,while the disc center(nucleus pulposus equivalent)showed dehydration and cellular *** manipulated BMD in young zebrafish by mutating sp7 and cathepsin K,leading to low and high BMD,***,we detected IVDD in both groups,demonstrating that low BMD does not protect against IVDD,and we found a strong correlation between high BMD and *** learning was applied to high-resolution synchrotron\iCJ image data to analyze osteocyte 3D lacunar distribution and morphology,revealing a role of sp7 in controlling the osteocyte lacunar 3D *** findings suggest potential avenues through which bone quality can be targeted to identify beneficial therapeutics for IVDD.

关键词： intervertebral degeneration protective

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