Muscular response to the first three months of deflazacort treatment in boys with Duchenne muscular dystrophy

L Jensen, S J Petersson, N O Illum, H C Laugaard-Jacobsen, T Thelle, L H Jørgensen, H D Schrøder

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

OBJECTIVE: Duchenne muscular dystrophy (DMD) patients are often treated with glucocorticoids; yet their precise molecular action remains unknown.

METHODS: We investigated muscle biopsies from nine boys with DMD (aged: 7,6±2,8 yrs.) collected before and after three months of deflazacort treatment and compared them to eight healthy boys (aged: 5,3±2,4 yrs.). mRNA transcripts involved in activation of satellite cells, myogenesis, regeneration, adipogenesis, muscle growth and tissue inflammation were assessed. Serum creatine kinase (CK) levels and muscle protein expression by immunohistochemistry of selected targets were also analysed.

RESULTS: Transcript levels for ADIPOQ, CD68, CDH15, FGF2, IGF1R, MYF5, MYF6, MYH8, MYOD, PAX7, and TNFα were significantly different in untreated patients vs. normal muscle (p⟨0.05). Linear tests for trend indicated that the expression levels of treated patients were approaching normal values (p⟨0.05) following treatment (towards an increase; CDH15, C-MET, DLK1, FGF2, IGF1R, MYF5, MYF6, MYOD, PAX7; towards a decrease: CD68, MYH8, TNFα). Treatment reduced CK levels (p⟨0.05), but we observed no effect on muscle protein expression.

CONCLUSIONS: This study provides insight into the molecular actions of glucocorticoids in DMD at the mRNA level, and we show that multiple regulatory pathways are influenced. This information can be important in the development of new treatments.

Original languageEnglish
JournalJournal of Musculoskeletal and Neuronal Interactions
Volume17
Issue number2
Pages (from-to)8-18
ISSN1108-7161
Publication statusPublished - 1. Jun 2017

Fingerprint

Duchenne Muscular Dystrophy
Muscle Proteins
Fibroblast Growth Factor 2
Muscles
Glucocorticoids
No-Observed-Adverse-Effect Level
Adipogenesis
Messenger RNA
Muscle Development
Reference Values
deflazacort
Growth
Serum

Keywords

  • Journal Article

Cite this

@article{6bc8dfa6f7b941afb129bf50f199d0dd,
title = "Muscular response to the first three months of deflazacort treatment in boys with Duchenne muscular dystrophy",
abstract = "OBJECTIVE: Duchenne muscular dystrophy (DMD) patients are often treated with glucocorticoids; yet their precise molecular action remains unknown.METHODS: We investigated muscle biopsies from nine boys with DMD (aged: 7,6±2,8 yrs.) collected before and after three months of deflazacort treatment and compared them to eight healthy boys (aged: 5,3±2,4 yrs.). mRNA transcripts involved in activation of satellite cells, myogenesis, regeneration, adipogenesis, muscle growth and tissue inflammation were assessed. Serum creatine kinase (CK) levels and muscle protein expression by immunohistochemistry of selected targets were also analysed.RESULTS: Transcript levels for ADIPOQ, CD68, CDH15, FGF2, IGF1R, MYF5, MYF6, MYH8, MYOD, PAX7, and TNFα were significantly different in untreated patients vs. normal muscle (p⟨0.05). Linear tests for trend indicated that the expression levels of treated patients were approaching normal values (p⟨0.05) following treatment (towards an increase; CDH15, C-MET, DLK1, FGF2, IGF1R, MYF5, MYF6, MYOD, PAX7; towards a decrease: CD68, MYH8, TNFα). Treatment reduced CK levels (p⟨0.05), but we observed no effect on muscle protein expression.CONCLUSIONS: This study provides insight into the molecular actions of glucocorticoids in DMD at the mRNA level, and we show that multiple regulatory pathways are influenced. This information can be important in the development of new treatments.",
keywords = "Journal Article",
author = "L Jensen and Petersson, {S J} and Illum, {N O} and Laugaard-Jacobsen, {H C} and T Thelle and J{\o}rgensen, {L H} and Schr{\o}der, {H D}",
year = "2017",
month = "6",
day = "1",
language = "English",
volume = "17",
pages = "8--18",
journal = "Journal of Musculoskeletal and Neuronal Interactions",
issn = "1108-7161",
publisher = "The/International Society of Musculoskeletal and Neuronal Interactions",
number = "2",

}

Muscular response to the first three months of deflazacort treatment in boys with Duchenne muscular dystrophy. / Jensen, L; Petersson, S J; Illum, N O; Laugaard-Jacobsen, H C; Thelle, T; Jørgensen, L H; Schrøder, H D.

In: Journal of Musculoskeletal and Neuronal Interactions, Vol. 17, No. 2, 01.06.2017, p. 8-18.

Research output: Contribution to journalJournal articleResearchpeer-review

TY - JOUR

T1 - Muscular response to the first three months of deflazacort treatment in boys with Duchenne muscular dystrophy

AU - Jensen, L

AU - Petersson, S J

AU - Illum, N O

AU - Laugaard-Jacobsen, H C

AU - Thelle, T

AU - Jørgensen, L H

AU - Schrøder, H D

PY - 2017/6/1

Y1 - 2017/6/1

N2 - OBJECTIVE: Duchenne muscular dystrophy (DMD) patients are often treated with glucocorticoids; yet their precise molecular action remains unknown.METHODS: We investigated muscle biopsies from nine boys with DMD (aged: 7,6±2,8 yrs.) collected before and after three months of deflazacort treatment and compared them to eight healthy boys (aged: 5,3±2,4 yrs.). mRNA transcripts involved in activation of satellite cells, myogenesis, regeneration, adipogenesis, muscle growth and tissue inflammation were assessed. Serum creatine kinase (CK) levels and muscle protein expression by immunohistochemistry of selected targets were also analysed.RESULTS: Transcript levels for ADIPOQ, CD68, CDH15, FGF2, IGF1R, MYF5, MYF6, MYH8, MYOD, PAX7, and TNFα were significantly different in untreated patients vs. normal muscle (p⟨0.05). Linear tests for trend indicated that the expression levels of treated patients were approaching normal values (p⟨0.05) following treatment (towards an increase; CDH15, C-MET, DLK1, FGF2, IGF1R, MYF5, MYF6, MYOD, PAX7; towards a decrease: CD68, MYH8, TNFα). Treatment reduced CK levels (p⟨0.05), but we observed no effect on muscle protein expression.CONCLUSIONS: This study provides insight into the molecular actions of glucocorticoids in DMD at the mRNA level, and we show that multiple regulatory pathways are influenced. This information can be important in the development of new treatments.

AB - OBJECTIVE: Duchenne muscular dystrophy (DMD) patients are often treated with glucocorticoids; yet their precise molecular action remains unknown.METHODS: We investigated muscle biopsies from nine boys with DMD (aged: 7,6±2,8 yrs.) collected before and after three months of deflazacort treatment and compared them to eight healthy boys (aged: 5,3±2,4 yrs.). mRNA transcripts involved in activation of satellite cells, myogenesis, regeneration, adipogenesis, muscle growth and tissue inflammation were assessed. Serum creatine kinase (CK) levels and muscle protein expression by immunohistochemistry of selected targets were also analysed.RESULTS: Transcript levels for ADIPOQ, CD68, CDH15, FGF2, IGF1R, MYF5, MYF6, MYH8, MYOD, PAX7, and TNFα were significantly different in untreated patients vs. normal muscle (p⟨0.05). Linear tests for trend indicated that the expression levels of treated patients were approaching normal values (p⟨0.05) following treatment (towards an increase; CDH15, C-MET, DLK1, FGF2, IGF1R, MYF5, MYF6, MYOD, PAX7; towards a decrease: CD68, MYH8, TNFα). Treatment reduced CK levels (p⟨0.05), but we observed no effect on muscle protein expression.CONCLUSIONS: This study provides insight into the molecular actions of glucocorticoids in DMD at the mRNA level, and we show that multiple regulatory pathways are influenced. This information can be important in the development of new treatments.

KW - Journal Article

M3 - Journal article

VL - 17

SP - 8

EP - 18

JO - Journal of Musculoskeletal and Neuronal Interactions

JF - Journal of Musculoskeletal and Neuronal Interactions

SN - 1108-7161

IS - 2

ER -