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Paraspinal Muscle Ladybird Homeobox 1 (LBX1) in adolescent idiopathic scoliosis: a cross-sectional study.

Abstract

BACKGROUND CONTEXT

Adolescent idiopathic scoliosis (AIS) is the leading cause of spinal deformity in adolescents globally. Recent evidence from Genome-Wide Association Studies has implicated variants in or near the Ladybird Homeobox 1 (LBX1) gene, encoding the ladybird homeobox 1 transcription factor, in AIS development. This gene plays a critical role in guiding embryonic neurogenesis and myogenesis and is vital in muscle mass determination. Despite the confirmation of the role for LBX1 gene variants in the development of AIS, the biological basis of LBX1 contribution to AIS remains mostly unknown.

PURPOSE

To investigate the potential role of LBX1 in driving spinal curving, curve laterality, and progression through muscle-based mechanisms in AIS patients by analyzing its gene and protein expression.

STUDY DESIGN

This is a cross-sectional study using clinical data and biological samples from the Immunometabolic Connections to Scoliosis study (ICONS study).

PATIENT SAMPLE

Twenty-five patients with AIS provided informed consent. Paraspinal muscle biopsies from the maximal points of concavity and convexity for gene expression and protein analysis were obtained at the start of corrective spinal surgery.

OUTCOME MEASURES

The outcome measures included the detection of paraspinal muscle LBX1 mRNA abundance and LBX1 protein expression and the correlation of the latter with age, sex, and curve severity.

METHODS

The measurement of mRNA abundance was done using Quantitative Real-Time Polymerase Chain Reaction (qRT-PCR). Additionally, protein lysates from the biopsied muscle samples were probed with a monoclonal LBX1 antibody to compare the muscle protein levels on either side of the scoliotic curve by western blot. This study received funding from the Division of Orthopedics, Department of Surgery, McMaster University, Hamilton, Ontario, Canada ($39,900 CAN for 2 years). The authors have no conflicts of interest to disclose.

RESULTS

LBX1 mRNA abundance (concave 2.98±0.87, convex 3.40±1.10, p value 0.73) and protein expression (concave 1.20±0.13, convex 1.21±0.10, p value 0.43) were detected on both sides of the scoliotic curve at equivalent levels. The expression of LBX1 protein did not correlate with age (concave: correlation coefficient 0.32, p value 0.12; convex: correlation coefficient 0.08, p value 0.69), sex (concave: correlation coefficient -0.03, p value 0.08; convex: correlation coefficient 0.07, p value 0.72), or the severity of spinal curving measured using the Cobb angle (concave: correlation coefficient -0.16, p value 0.45; convex: correlation coefficient -0.08, p value 0.69).

CONCLUSIONS

LBX1 is expressed in erector spinae muscles, and its levels are equal in muscles on both sides of the scoliotic curve in AIS. The expression of LBX1 on the convex and concave sides of the scoliotic curve did not correlate with age, sex, or the severity of spinal curving. The molecular mechanisms by which LBX1contributes to the development and propagation of AIS need to be explored further in muscle and other tissues.

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  • Authors+Show Affiliations

    ,

    Department of Pediatrics, McMaster University, Hamilton, Ontario, Canada; Division of Pediatric Endocrinology, McMaster Children's Hospital, Hamilton, Ontario, Canada.

    ,

    Department of Pediatrics, McMaster University, Hamilton, Ontario, Canada; Division of Pediatric Endocrinology, McMaster Children's Hospital, Hamilton, Ontario, Canada.

    ,

    Division of Orthopedics, Department of Surgery, McMaster University, Hamilton, Ontario, Canada.

    ,

    Division of Orthopedics, Department of Surgery, McMaster University, Hamilton, Ontario, Canada.

    ,

    Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, Ontario, Canada; Department of Anesthesia, McMaster University, Hamilton, Ontario, Canada; Centre for Evaluation of Medicines, St. Joseph's Health Care, Hamilton, Ontario, Canada; Biostatistics Unit, St Joseph's Healthcare-Hamilton, Hamilton, Ontario, Canada.

    ,

    Department of Medicine, McMaster University, Hamilton, Ontario, Canada.

    Department of Pediatrics, McMaster University, Hamilton, Ontario, Canada; Division of Pediatric Endocrinology, McMaster Children's Hospital, Hamilton, Ontario, Canada; Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, Ontario, Canada. Electronic address: samaanc@mcmaster.ca.

    Source

    Pub Type(s)

    Journal Article

    Language

    eng

    PubMed ID

    31202838

    Citation

    Jennings, William, et al. "Paraspinal Muscle Ladybird Homeobox 1 (LBX1) in Adolescent Idiopathic Scoliosis: a Cross-sectional Study." The Spine Journal : Official Journal of the North American Spine Society, 2019.
    Jennings W, Hou M, Perterson D, et al. Paraspinal Muscle Ladybird Homeobox 1 (LBX1) in adolescent idiopathic scoliosis: a cross-sectional study. Spine J. 2019.
    Jennings, W., Hou, M., Perterson, D., Missiuna, P., Thabane, L., Tarnopolsky, M., & Samaan, M. C. (2019). Paraspinal Muscle Ladybird Homeobox 1 (LBX1) in adolescent idiopathic scoliosis: a cross-sectional study. The Spine Journal : Official Journal of the North American Spine Society, doi:10.1016/j.spinee.2019.06.014.
    Jennings W, et al. Paraspinal Muscle Ladybird Homeobox 1 (LBX1) in Adolescent Idiopathic Scoliosis: a Cross-sectional Study. Spine J. 2019 Jun 14; PubMed PMID: 31202838.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Paraspinal Muscle Ladybird Homeobox 1 (LBX1) in adolescent idiopathic scoliosis: a cross-sectional study. AU - Jennings,William, AU - Hou,Maggie, AU - Perterson,Devin, AU - Missiuna,Paul, AU - Thabane,Lehana, AU - Tarnopolsky,Mark, AU - Samaan,M Constantine, Y1 - 2019/06/14/ PY - 2019/02/22/received PY - 2019/06/10/revised PY - 2019/06/11/accepted PY - 2019/6/17/pubmed PY - 2019/6/17/medline PY - 2019/6/17/entrez KW - Adolescent idiopathic scoliosis KW - ICONS study KW - Ladybird Homeobox 1 KW - paraspinal muscle JF - The spine journal : official journal of the North American Spine Society JO - Spine J N2 - BACKGROUND CONTEXT: Adolescent idiopathic scoliosis (AIS) is the leading cause of spinal deformity in adolescents globally. Recent evidence from Genome-Wide Association Studies has implicated variants in or near the Ladybird Homeobox 1 (LBX1) gene, encoding the ladybird homeobox 1 transcription factor, in AIS development. This gene plays a critical role in guiding embryonic neurogenesis and myogenesis and is vital in muscle mass determination. Despite the confirmation of the role for LBX1 gene variants in the development of AIS, the biological basis of LBX1 contribution to AIS remains mostly unknown. PURPOSE: To investigate the potential role of LBX1 in driving spinal curving, curve laterality, and progression through muscle-based mechanisms in AIS patients by analyzing its gene and protein expression. STUDY DESIGN: This is a cross-sectional study using clinical data and biological samples from the Immunometabolic Connections to Scoliosis study (ICONS study). PATIENT SAMPLE: Twenty-five patients with AIS provided informed consent. Paraspinal muscle biopsies from the maximal points of concavity and convexity for gene expression and protein analysis were obtained at the start of corrective spinal surgery. OUTCOME MEASURES: The outcome measures included the detection of paraspinal muscle LBX1 mRNA abundance and LBX1 protein expression and the correlation of the latter with age, sex, and curve severity. METHODS: The measurement of mRNA abundance was done using Quantitative Real-Time Polymerase Chain Reaction (qRT-PCR). Additionally, protein lysates from the biopsied muscle samples were probed with a monoclonal LBX1 antibody to compare the muscle protein levels on either side of the scoliotic curve by western blot. This study received funding from the Division of Orthopedics, Department of Surgery, McMaster University, Hamilton, Ontario, Canada ($39,900 CAN for 2 years). The authors have no conflicts of interest to disclose. RESULTS: LBX1 mRNA abundance (concave 2.98±0.87, convex 3.40±1.10, p value 0.73) and protein expression (concave 1.20±0.13, convex 1.21±0.10, p value 0.43) were detected on both sides of the scoliotic curve at equivalent levels. The expression of LBX1 protein did not correlate with age (concave: correlation coefficient 0.32, p value 0.12; convex: correlation coefficient 0.08, p value 0.69), sex (concave: correlation coefficient -0.03, p value 0.08; convex: correlation coefficient 0.07, p value 0.72), or the severity of spinal curving measured using the Cobb angle (concave: correlation coefficient -0.16, p value 0.45; convex: correlation coefficient -0.08, p value 0.69). CONCLUSIONS: LBX1 is expressed in erector spinae muscles, and its levels are equal in muscles on both sides of the scoliotic curve in AIS. The expression of LBX1 on the convex and concave sides of the scoliotic curve did not correlate with age, sex, or the severity of spinal curving. The molecular mechanisms by which LBX1contributes to the development and propagation of AIS need to be explored further in muscle and other tissues. SN - 1878-1632 UR - https://www.unboundmedicine.com/medline/citation/31202838/Paraspinal_Muscle_Ladybird_Homeobox_1_(LBX1)_in_Adolescent_Idiopathic_Scoliosis:_A_cross-sectional_study L2 - https://linkinghub.elsevier.com/retrieve/pii/S1529-9430(19)30809-5 DB - PRIME DP - Unbound Medicine ER -