Gene expressions in cerebral palsy subjects reveal structural and functional changes in the gastrocnemius muscle that are closely associated with passive muscle stiffness
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Gene expressions in cerebral palsy subjects reveal structural and functional changes in the gastrocnemius muscle that are closely associated with passive muscle stiffness. / Pingel, Jessica; Kampmann, Marie Louise; Andersen, Jeppe Dyrberg; Wong, Christian; Døssing, Simon; Børsting, Claus; Nielsen, Jens Bo.
In: Cell and Tissue Research, Vol. 384, 2021, p. 513–526.Research output: Contribution to journal › Journal article › Research › peer-review
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T1 - Gene expressions in cerebral palsy subjects reveal structural and functional changes in the gastrocnemius muscle that are closely associated with passive muscle stiffness
AU - Pingel, Jessica
AU - Kampmann, Marie Louise
AU - Andersen, Jeppe Dyrberg
AU - Wong, Christian
AU - Døssing, Simon
AU - Børsting, Claus
AU - Nielsen, Jens Bo
PY - 2021
Y1 - 2021
N2 - Cerebral palsy (CP) is a non-progressive motor disorder that affects posture and gait due to contracture development. The purpose of this study is to analyze a possible relation between muscle stiffness and gene expression levels in muscle tissue of children with CP. Next-generation sequencing (NGS) of gene transcripts was carried out in muscle biopsies from gastrocnemius muscle (n = 13 children with CP and n = 13 typical developed (TD) children). Passive stiffness of the ankle plantarflexors was measured. Structural changes of the basement membranes and the sarcomere length were measured. Twelve pre-defined gene target sub-categories of muscle function, structure and metabolism showed significant differences between muscle tissue of CP and TD children. Passive stiffness was significantly correlated to gene expression levels of HSPG2 (p = 0.02; R2 = 0.67), PRELP (p = 0.002; R2 = 0.84), RYR3 (p = 0.04; R2 = 0.66), C COL5A3 (p = 0.0007; R2 = 0.88), ASPH (p = 0.002; R2 = 0.82) and COL4A6 (p = 0.03; R2 = 0.97). Morphological differences in the basement membrane were observed between children with CP and TD children. The sarcomere length was significantly increased in children with CP when compared with TD (p = 0.04). These findings show that gene targets in the categories: calcium handling, basement membrane and collagens, were significantly correlated to passive muscle stiffness. A Reactome pathway analysis showed that pathways involved in DNA repair, ECM proteoglycans and ion homeostasis were amongst the most upregulated pathways in CP, while pathways involved in collagen fibril crosslinking, collagen fibril assembly and collagen turnover were amongst the most downregulated pathways when compared with TD children. These results underline that contracture formation and motor impairment in CP is an interplay between multiple factors.
AB - Cerebral palsy (CP) is a non-progressive motor disorder that affects posture and gait due to contracture development. The purpose of this study is to analyze a possible relation between muscle stiffness and gene expression levels in muscle tissue of children with CP. Next-generation sequencing (NGS) of gene transcripts was carried out in muscle biopsies from gastrocnemius muscle (n = 13 children with CP and n = 13 typical developed (TD) children). Passive stiffness of the ankle plantarflexors was measured. Structural changes of the basement membranes and the sarcomere length were measured. Twelve pre-defined gene target sub-categories of muscle function, structure and metabolism showed significant differences between muscle tissue of CP and TD children. Passive stiffness was significantly correlated to gene expression levels of HSPG2 (p = 0.02; R2 = 0.67), PRELP (p = 0.002; R2 = 0.84), RYR3 (p = 0.04; R2 = 0.66), C COL5A3 (p = 0.0007; R2 = 0.88), ASPH (p = 0.002; R2 = 0.82) and COL4A6 (p = 0.03; R2 = 0.97). Morphological differences in the basement membrane were observed between children with CP and TD children. The sarcomere length was significantly increased in children with CP when compared with TD (p = 0.04). These findings show that gene targets in the categories: calcium handling, basement membrane and collagens, were significantly correlated to passive muscle stiffness. A Reactome pathway analysis showed that pathways involved in DNA repair, ECM proteoglycans and ion homeostasis were amongst the most upregulated pathways in CP, while pathways involved in collagen fibril crosslinking, collagen fibril assembly and collagen turnover were amongst the most downregulated pathways when compared with TD children. These results underline that contracture formation and motor impairment in CP is an interplay between multiple factors.
KW - Cerebral palsy
KW - Contractures
KW - mRNA
KW - Passive stiffness
KW - Sarcomere
U2 - 10.1007/s00441-020-03399-z
DO - 10.1007/s00441-020-03399-z
M3 - Journal article
C2 - 33515289
AN - SCOPUS:85099952827
VL - 384
SP - 513
EP - 526
JO - Cell and Tissue Research
JF - Cell and Tissue Research
SN - 0302-766X
ER -
ID: 257279878