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

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 

机构地区：[1]School of Physiology,Pharmacology and Neuroscience,Biomedical Sciences,University of Bristol,Bristol,UK [2]School of Physics,HH Wills Physics Laboratory,University of Bristol,Bristol,UK [3]Centre for Nanoscience and Quantum Information,University of Bristol,Bristol,UK [4]Bristol Centre for Functional Nanomaterials,University of Bristol,Bristol,UK [5]Department of Anthropology and Archaeology,University of Bristol,Bristol,UK [6]Department of Mechanical Engineering,University of Bristol,Bristol,UK [7]Clinical Genetics Department,Human Genetics and Genome Research Division,Center of Excellence for Human Genetics,National Research Centre,Cairo,Egypt [8]lnstituto de Investigaciones,Biomedicas de Madrid,and Ciber de Enfermedades Raras(CIBERER),Madrid,Spain [9]Wolfson Bioimaging Facility,Biomedical Sciences,University of Bristol,Bristol,UK [10]School of Chemistry,University of Bristol,Bristol,UK [11]Evolutionary Developmental Biology,Department of Biology,Ghent University,Ghent,Belgium

出　　处：《Bone Research》2021年第4期521-536,共16页骨研究（英文版）

摘　　要：Back pain is a common condition with a high social impact and represents a global health burden.Intervertebral disc disease(IVDD)is one of the major causes of back pain;no therapeutics are currently available to reverse this disease.The 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 IVDD.Functional studies to evaluate the influence of genetic components of BMD in IVDD could highlight opportunities for drug development and repurposing.By taking a holistic 3D approach,we established an aging zebrafish model for spontaneous IVDD.Increased BMD in aging,detected by automated computational analysis,is caused by bone deformities at the endplates.However,aged zebrafish spines showed changes in bone morphology,microstructure,mineral heterogeneity,and increased fragility that resembled osteoporosis.Elements 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 abnormalities.We manipulated BMD in young zebrafish by mutating sp7 and cathepsin K,leading to low and high BMD,respectively.Remarkably,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 IVDD.Deep 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 profile.Our findings suggest potential avenues through which bone quality can be targeted to identify beneficial therapeutics for IVDD.

关 键 词：INTERVERTEBRAL DEGENERATION protective 

分 类 号：R681.53[医药卫生—骨科学]