Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Whole Genome Expression Profiling of Semitendinosus Tendons from Children with Diplegic and Tetraplegic Cerebral Palsy

Version 1 : Received: 29 August 2023 / Approved: 29 August 2023 / Online: 30 August 2023 (10:14:08 CEST)

A peer-reviewed article of this Preprint also exists.

Nemska, S.; Serio, S.; Larcher, V.; Beltrame, G.; Portinaro, N.M.; Bang, M.-L. Whole Genome Expression Profiling of Semitendinosus Tendons from Children with Diplegic and Tetraplegic Cerebral Palsy. Biomedicines 2023, 11, 2918. Nemska, S.; Serio, S.; Larcher, V.; Beltrame, G.; Portinaro, N.M.; Bang, M.-L. Whole Genome Expression Profiling of Semitendinosus Tendons from Children with Diplegic and Tetraplegic Cerebral Palsy. Biomedicines 2023, 11, 2918.

Abstract

Cerebral palsy (CP) is the most common movement disorder in children with a prevalence rang-ing from 1.5 to 4 per 1000 live births. CP is caused by a non-progressive lesion of the developing brain, leading to progressive alterations of the musculoskeletal system, including spasticity, often leading to the development of fixed contractures, necessitating tendon lengthening surgery. Total RNA-sequencing analysis was performed on semitendinosus tendons from diplegic and tetraple-gic CP patients subjected to tendon lengthening surgery compared to control patients undergoing anterior cruciate ligament reconstructive surgery. Tetraplegic CP patients showed increased ex-pression of genes implicated in collagen synthesis and extracellular matrix (ECM) turnover, while only minor changes were observed in diplegic CP patients. In addition, tendons from tetra-plegic CP patients showed an enrichment for upregulated genes involved in vesicle-mediated transport and downregulated genes involved in cytokine and apoptotic signaling. Overall, our results indicate increased ECM turnover with increased net synthesis of collagen in tetraplegic CP patients without activation of inflammatory and apoptotic pathways similar to observations in athletes where ECM remodeling results in increased tendon stiffness and tensile strength. Never-theless, the resulting increased tendon stiffness is an important issue in clinical practice, where surgery is often required to restore joint mobility.

Keywords

Cerebral palsy; tendons; extracellular matrix; gene expression; RNA-sequencing

Subject

Biology and Life Sciences, Biochemistry and Molecular Biology

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