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Slow twitch paraspinal muscle dysregulation in adolescent idiopathic scoliosis exhibiting HIF‐2α misexpression

BACKGROUND: Adolescent idiopathic scoliosis (AIS) refers to a three‐dimensional spinal deformity which has a typical onset during adolescence. In most cases, the cause of the deformity cannot be clearly identified. Unbalanced paraspinal muscle activity in AIS patients was reported and hypoxia was im...

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Autores principales: Tam, Wai Kit, Cheung, Jason P. Y., Koljonen, Paul A., Kwan, Kenny Y. H., Cheung, Kenneth M.C., Leung, Victor Y. L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley & Sons, Inc. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9799082/
https://www.ncbi.nlm.nih.gov/pubmed/36601371
http://dx.doi.org/10.1002/jsp2.1227
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author Tam, Wai Kit
Cheung, Jason P. Y.
Koljonen, Paul A.
Kwan, Kenny Y. H.
Cheung, Kenneth M.C.
Leung, Victor Y. L.
author_facet Tam, Wai Kit
Cheung, Jason P. Y.
Koljonen, Paul A.
Kwan, Kenny Y. H.
Cheung, Kenneth M.C.
Leung, Victor Y. L.
author_sort Tam, Wai Kit
collection PubMed
description BACKGROUND: Adolescent idiopathic scoliosis (AIS) refers to a three‐dimensional spinal deformity which has a typical onset during adolescence. In most cases, the cause of the deformity cannot be clearly identified. Unbalanced paraspinal muscle activity in AIS patients was reported and hypoxia was implicated to regulate myogenesis. This study aims to investigate the association between myogenesis/muscle toning and HIF‐αs activity in the pathogenesis of AIS. METHODS: HIF‐αs expression was examined by enzyme‐linked immunosorbent assay and western blot in paraspinal myoblasts isolated from 18 subjects who underwent deformity correction surgery. QPCR was conducted to measure the gene expression levels of perinatal muscle fiber markers MYH3, MYH8; slow twitch muscle fiber markers MHY7; fast twitch muscle fiber markers MYH4; and myogenic regulatory factors MYF5 and MYOG. Slow and fast twitch muscle fiber composition in concave/convex paraspinal musculature of AIS subjects was evaluated by immunostaining of myosin heavy chain type I (MyHC I) and myosin heavy chain type II (MyHC II). RESULTS: Reduced HIF‐2α induction under hypoxia was found in paraspinal myoblast culture of 33% AIS subjects. We detected a suppression of perinatal and slow twitch muscle fiber associated genes, but not fast twitch muscle fiber‐associated genes and myogenic regulatory factors in HIF‐2α misexpressed AIS myoblasts. Distinct reduction of slow twitch muscle fiber was evidenced in convex paraspinal musculature, suggesting an asymmetric expression of slow twitch muscle fiber in HIF‐2α misexpressed AIS patients. CONCLUSIONS: This study indicates an association of abnormal HIF‐2α expression in paraspinal myoblasts and a disproportionate slow twitch muscle fiber content in the convexity of the curvature in a subset of AIS subjects, suggesting HIF‐2α dysregulation as a possible risk factor for AIS. The role of HIF‐2α in paraspinal muscle function during spinal growth and its relevance in AIS prognosis warrants further investigation.
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spelling pubmed-97990822023-01-03 Slow twitch paraspinal muscle dysregulation in adolescent idiopathic scoliosis exhibiting HIF‐2α misexpression Tam, Wai Kit Cheung, Jason P. Y. Koljonen, Paul A. Kwan, Kenny Y. H. Cheung, Kenneth M.C. Leung, Victor Y. L. JOR Spine Research Articles BACKGROUND: Adolescent idiopathic scoliosis (AIS) refers to a three‐dimensional spinal deformity which has a typical onset during adolescence. In most cases, the cause of the deformity cannot be clearly identified. Unbalanced paraspinal muscle activity in AIS patients was reported and hypoxia was implicated to regulate myogenesis. This study aims to investigate the association between myogenesis/muscle toning and HIF‐αs activity in the pathogenesis of AIS. METHODS: HIF‐αs expression was examined by enzyme‐linked immunosorbent assay and western blot in paraspinal myoblasts isolated from 18 subjects who underwent deformity correction surgery. QPCR was conducted to measure the gene expression levels of perinatal muscle fiber markers MYH3, MYH8; slow twitch muscle fiber markers MHY7; fast twitch muscle fiber markers MYH4; and myogenic regulatory factors MYF5 and MYOG. Slow and fast twitch muscle fiber composition in concave/convex paraspinal musculature of AIS subjects was evaluated by immunostaining of myosin heavy chain type I (MyHC I) and myosin heavy chain type II (MyHC II). RESULTS: Reduced HIF‐2α induction under hypoxia was found in paraspinal myoblast culture of 33% AIS subjects. We detected a suppression of perinatal and slow twitch muscle fiber associated genes, but not fast twitch muscle fiber‐associated genes and myogenic regulatory factors in HIF‐2α misexpressed AIS myoblasts. Distinct reduction of slow twitch muscle fiber was evidenced in convex paraspinal musculature, suggesting an asymmetric expression of slow twitch muscle fiber in HIF‐2α misexpressed AIS patients. CONCLUSIONS: This study indicates an association of abnormal HIF‐2α expression in paraspinal myoblasts and a disproportionate slow twitch muscle fiber content in the convexity of the curvature in a subset of AIS subjects, suggesting HIF‐2α dysregulation as a possible risk factor for AIS. The role of HIF‐2α in paraspinal muscle function during spinal growth and its relevance in AIS prognosis warrants further investigation. John Wiley & Sons, Inc. 2022-11-02 /pmc/articles/PMC9799082/ /pubmed/36601371 http://dx.doi.org/10.1002/jsp2.1227 Text en © 2022 The Authors. JOR Spine published by Wiley Periodicals LLC on behalf of Orthopaedic Research Society. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Research Articles
Tam, Wai Kit
Cheung, Jason P. Y.
Koljonen, Paul A.
Kwan, Kenny Y. H.
Cheung, Kenneth M.C.
Leung, Victor Y. L.
Slow twitch paraspinal muscle dysregulation in adolescent idiopathic scoliosis exhibiting HIF‐2α misexpression
title Slow twitch paraspinal muscle dysregulation in adolescent idiopathic scoliosis exhibiting HIF‐2α misexpression
title_full Slow twitch paraspinal muscle dysregulation in adolescent idiopathic scoliosis exhibiting HIF‐2α misexpression
title_fullStr Slow twitch paraspinal muscle dysregulation in adolescent idiopathic scoliosis exhibiting HIF‐2α misexpression
title_full_unstemmed Slow twitch paraspinal muscle dysregulation in adolescent idiopathic scoliosis exhibiting HIF‐2α misexpression
title_short Slow twitch paraspinal muscle dysregulation in adolescent idiopathic scoliosis exhibiting HIF‐2α misexpression
title_sort slow twitch paraspinal muscle dysregulation in adolescent idiopathic scoliosis exhibiting hif‐2α misexpression
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9799082/
https://www.ncbi.nlm.nih.gov/pubmed/36601371
http://dx.doi.org/10.1002/jsp2.1227
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