Lucas R Smith1, Rajeswari Pichika2, Rachel C Meza3,4, Allison R Gillies3, Marwan N Baliki2, Henry G Chambers5, Richard L Lieber2,3,6. 1. Departments of Neurobiology, Physiology, and Behavior and Physical Medicine and Rehabilitation, University of California, Davis, CA, USA. 2. Shirley Ryan AbilityLab and Department of Physical Medicine and Rehabilitation, Northwestern University, Chicago, IL, USA. 3. Department of Orthopaedic Surgery, University of California San Diego, La Jolla, CA, USA. 4. Department of Biology, University of California San Diego, La Jolla, CA, USA. 5. Department of Orthopaedics, Rady Children's Hospital, San Diego, CA, USA. 6. Research Service, Hines V.A. Medical Center, Maywood, IL, USA.
Abstract
Purpose: Joint contractures in children with cerebral palsy contain muscle tissue that is mechanically stiffer with higher collagen content than typically developing children. Interestingly, the correlation between collagen content and stiffness is weak. To date, no data are available on collagen types or other extracellular matrix proteins in these muscles, nor any information regarding their function. Thus, our purpose was to measure specific extracellular protein composition in cerebral palsy and typically developing human muscles along with structural aspects of extracellular matrix architecture to determine the extent to which these explain mechanical properties. Materials and Methods: Biopsies were collected from children with cerebral palsy undergoing muscle lengthening procedures and typically developing children undergoing anterior cruciate ligament reconstruction. Tissue was prepared for the determination of collagen types I, III, IV, and VI, proteoglycan, biglycan, decorin, hyaluronic acid/uronic acid and collagen crosslinking. Results: All collagen types increased in cerebral palsy along with pyridinoline crosslinks, total proteoglycan, and uronic acid. In all cases, type I or total collagen and total proteoglycan were positive predictors, while biglycan was a negative predictor of stiffness. Together these parameters accounted for a greater degree of variance within groups than across groups, demonstrating an altered relationship between extracellular matrix and stiffness with cerebral palsy. Further, stereological analysis revealed a significant increase in collagen fibrils organized in cables and an increased volume fraction of fibroblasts in CP muscle. Conclusions: These data demonstrate a novel adaptation of muscle extracellular matrix in children with cerebral palsy that includes alterations in extracellular matrix protein composition and structure related to mechanical function.
Purpose: Joint contractures in children with cerebral palsy contain muscle tissue that is mechanically stiffer with higher collagen content than typically developing children. Interestingly, the correlation between collagen content and stiffness is weak. To date, no data are available on collagen types or other extracellular matrix proteins in these muscles, nor any information regarding their function. Thus, our purpose was to measure specific extracellular protein composition in cerebral palsy and typically developing human muscles along with structural aspects of extracellular matrix architecture to determine the extent to which these explain mechanical properties. Materials and Methods: Biopsies were collected from children with cerebral palsy undergoing muscle lengthening procedures and typically developing children undergoing anterior cruciate ligament reconstruction. Tissue was prepared for the determination of collagen types I, III, IV, and VI, proteoglycan, biglycan, decorin, hyaluronic acid/uronic acid and collagen crosslinking. Results: All collagen types increased in cerebral palsy along with pyridinoline crosslinks, total proteoglycan, and uronic acid. In all cases, type I or total collagen and total proteoglycan were positive predictors, while biglycan was a negative predictor of stiffness. Together these parameters accounted for a greater degree of variance within groups than across groups, demonstrating an altered relationship between extracellular matrix and stiffness with cerebral palsy. Further, stereological analysis revealed a significant increase in collagen fibrils organized in cables and an increased volume fraction of fibroblasts in CP muscle. Conclusions: These data demonstrate a novel adaptation of muscle extracellular matrix in children with cerebral palsy that includes alterations in extracellular matrix protein composition and structure related to mechanical function.
Authors: Guiyun Zhang; Shoujun Chen; Silvia Goldoni; Bennett W Calder; Holly C Simpson; Rick T Owens; David J McQuillan; Marian F Young; Renato V Iozzo; David E Birk Journal: J Biol Chem Date: 2009-01-09 Impact factor: 5.157
Authors: Kelsey A Robinson; Mei Sun; Carrie E Barnum; Stephanie N Weiss; Julianne Huegel; Snehal S Shetye; Linda Lin; Daniel Saez; Sheila M Adams; Renato V Iozzo; Louis J Soslowsky; David E Birk Journal: Matrix Biol Date: 2017-09-05 Impact factor: 11.583
Authors: Joline E Brandenburg; Sarah F Eby; Pengfei Song; Shirley Kingsley-Berg; William Bamlet; Gary C Sieck; Kai-Nan An Journal: Dev Med Child Neurol Date: 2016-07-04 Impact factor: 5.449
Authors: Daniel B Hoffman; Christiana J Raymond-Pope; Jacob R Sorensen; Benjamin T Corona; Sarah M Greising Journal: Connect Tissue Res Date: 2021-02-15 Impact factor: 3.417
Authors: Lin-Ya Hu; Cassidy J Mileti; Taryn Loomis; Sarah E Brashear; Sarah Ahmad; Rosemary R Chellakudam; Ross P Wohlgemuth; Marissa A Gionet-Gonzales; J Kent Leach; Lucas R Smith Journal: Am J Physiol Cell Physiol Date: 2021-06-30 Impact factor: 5.282