JOR SpinePub Date : 2026-04-22eCollection Date: 2026-06-01DOI: 10.1002/jsp2.70177
Edward C Moody, Emma M Wade, Shuji Mizumoto, Jeremy McCallum-Loudeac, Megan J Wilson
{"title":"Deletion of a <i>Pax1</i> Sex-Associated Genomic Region Associated With Adolescent Idiopathic Scoliosis Leads to Disc Degeneration, Instability, and Vertebral Rotation in Mice.","authors":"Edward C Moody, Emma M Wade, Shuji Mizumoto, Jeremy McCallum-Loudeac, Megan J Wilson","doi":"10.1002/jsp2.70177","DOIUrl":"10.1002/jsp2.70177","url":null,"abstract":"<p><strong>Background: </strong>Adolescent idiopathic scoliosis (AIS) is a complex spinal deformity characterized by three-dimensional curvature of the spine with an unknown etiology. Previous genome-wide association studies have identified a single-nucleotide polymorphism (rs6137473) located downstream of <i>PAX1,</i> which is significantly associated with female AIS risk.</p><p><strong>Methods: </strong>To investigate the role of this region in spinal development and AIS pathogenesis, we generated a mouse model with deletion of a nearby conserved sex-associated region (<i>Pax1</i>-SARΔ). Spines were examined by both micro-CT and histology. Gene expression analysis (by RNA-sequencing and quantitative PCR) was carried out on E12.5 and E18.5 developing spines. Glycosaminoglycan (GAG) content was also measured by high-performance liquid chromatography.</p><p><strong>Results: </strong>Micro-CT analysis revealed increased vertebral rotation at T4 in female <i>Pax1</i>-SARΔ mice at 4 months and at T9 in male <i>Pax1</i>-SARΔ mice at 6 months, along with kyphotic and lordotic sagittal curvatures. Histological examination revealed significant intervertebral disc degeneration, with the most severe changes observed in the female <i>Pax1</i>-SARΔ mice. GAG analysis found decreased chondroitin sulfate and dermatan sulfate content in male and female <i>Pax1</i>-SARΔ mice. Gene expression analysis at E12.5 showed upregulation of <i>Pax1, Stat3, Ar</i>, <i>Foxa2,</i> and <i>Nkx2.2</i>, while RNA-sequencing at E18.5 revealed sex-dependent changes in gene expression related to extracellular matrix components, immune and inflammatory responses, and scoliosis.</p><p><strong>Conclusion: </strong>These findings highlight the pivotal role of the <i>Pax1</i> sex-associated genomic region in the development and maintenance of functional cartilage, extracellular matrix integrity, and intervertebral disc health, offering insights into the mechanisms underlying spinal degeneration and instability in AIS.</p>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"9 ","pages":"e70177"},"PeriodicalIF":3.9,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13102530/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147772078","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
JOR SpinePub Date : 2026-04-15eCollection Date: 2026-06-01DOI: 10.1002/jsp2.70181
Clarissa LeVasseur, Sabreen Megherhi, Matthew Mesoros, Gina McKernan, Richard Warwose, William Donaldson, Joon Y Lee, Gwendolyn Sowa, William Anderst
{"title":"Larger Lumbar Vertebral Body Osteophyte Volume Is Associated With Older Age and a More Caudal Vertebral Level in Individuals With Chronic Low Back Pain.","authors":"Clarissa LeVasseur, Sabreen Megherhi, Matthew Mesoros, Gina McKernan, Richard Warwose, William Donaldson, Joon Y Lee, Gwendolyn Sowa, William Anderst","doi":"10.1002/jsp2.70181","DOIUrl":"10.1002/jsp2.70181","url":null,"abstract":"<p><strong>Background: </strong>Chronic low back pain (cLBP) is often accompanied by changes in lumbar spine bony morphology, including osteophyte growth. Knowledge of the volume and location of osteophytes could provide insight into habitual loading that may induce symptomatic disc degeneration and serve to guide treatment. The aim of this study was to develop an automated method to calculate osteophyte volume in lumbar vertebral bodies and to evaluate the relationships between osteophyte volume and vertebral level, age, and sex.</p><p><strong>Methods: </strong>Patients with cLBP received computed tomography (CT) scans of their entire lumbar spine. Lumbar bone models were created from the segmented CT scans. A Procrustes-based registration algorithm transformed vertebral bodies from a reference library of bones with no osteophytes to match the patient's vertebral bodies. The best-matched reference bone was then subtracted from the original bone to create a model of the osteophytes. Osteophyte volume and location were calculated from the model, and associations were explored between osteophyte volume, vertebral level, sex, and age. Regional differences in osteophyte volume were also evaluated.</p><p><strong>Results: </strong>The osteophyte identification algorithm was validated to have a bias of -4.7 mm<sup>3</sup> and accuracy of 109.7 mm<sup>3</sup>. Osteophyte volume increased an average of 147.8 mm<sup>3</sup> with each caudal vertebral level. Osteophyte volume was greater in men than in women and increased between 34.3 and 47.7 mm<sup>3</sup> with each year of age. The superior half of L1 and L2 had 20%-35% greater osteophyte volume than the inferior half.</p><p><strong>Conclusions: </strong>Osteophyte volume increased with more caudal vertebrae, was greater in men than in women, and increased by approximately 40 mm<sup>3</sup> with each year of age in 264 individuals with cLBP.</p>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"9 2","pages":"e70181"},"PeriodicalIF":3.9,"publicationDate":"2026-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13082879/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147698834","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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