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Intraoperative and Laboratory Studies of Human Skeletal Muscle Contractures

Weekly Seminar | Not Open to the Public
Who Should Attend: 


Skeletal muscle is a highly plastic tissue, responding both to level of use and amount of neural input. After cerebral palsy (CP) altered neural input can result in muscle weakness and even contractures. We have studied the mechanics and biology of muscle from children with wrist flexion contractures secondary to CP. Dramatic architectural changes are observed in these children whereby sarcomere lengths are dramatically altered relative to patients without upper motor neuron lesions.  This suggests dramatic alterations in the regulation of muscle growth in these children.  Biomechanical studies of isolated single muscle cells reveal an increased passive modulus and decreased resting sarcomere length suggesting alterations in the cellular cytoskeleton. Gene expression profiling reveals a number of “conflicting” biological pathways in spastic muscle. Specifically, this muscle adapts by altering processes related to extracellular matrix production, fiber type determination, fiber hypertrophy and myogenesis. These transcriptional adaptations are not characteristic of muscle adaptations observed in Duchenne muscular dystrophy or limb immobilization. Superimposed upon the dramatic biological and structural adaptations is a loss in the number of satellite cells that are located throughout the muscle. Even the remaining satellite cells have epigenetic changes that can dramatically influence our ability to rehabilitate these muscles. Recently, we have shown that several anti-cancer drugs are able to reverse these epigenetic changes, thus “rescuing” the satellite cells and promoting myogenesis. Taken together, these results support the notion that, while contracture formation is multifactorial and neural in origin, significant structural alterations in muscle also occur. An understanding of the specific changes that occur in the muscle and extracellular matrix may facilitate the development of new conservative or surgical therapies for this condition.

Dr. Richard Lieber's Figure


Sudarshan Dayanidhi, Matthew C Kinney, Peter B Dykstra, Richard L Lieber
Does a Reduced Number of Muscle Stem Cells Impair the Addition of Sarcomeres and Recovery from a Skeletal Muscle Contracture? A Transgenic Mouse Model
Clin Orthop Relat Res. 2020 Apr;478(4):886-899. doi: 10.1097/CORR.0000000000001134.
Lydia A Sibley, Nicole Broda, Wendy R Gross, Austin F Menezes, Ryan B Embry, Vineeta T Swaroop, Henry G Chambers, Matthew J Schipma, Richard L Lieber, Andrea A Domenighetti
Differential DNA methylation and transcriptional signatures characterize impairment of muscle stem cells in pediatric human muscle contractures after brain injury
FASEB J. 2021 Oct;35(10):e21928. doi: 10.1096/fj.202100649R.
Richard L Lieber, Jan Fridén
Muscle contracture and passive mechanics in cerebral palsy
J Appl Physiol (1985). 2019 May 1;126(5):1492-1501. doi: 10.1152/japplphysiol.00278.2018. Epub 2018 Dec 20.


Tuesday, December 6, 2022 - 12:30pm


Conference Room: 
Billings Building – Rosedale & Zoom

More Information

Darlene White

Research Methods: 
Gene Expression, Epigenetics