image: 3-D reconstruction of a collagen cable (yellow) and collagen-producing cell (blue). view more
Credit: Dr. Allison Gillies and Dr. Richard Lieber
Eight million people per year in the UK suffer from muscular diseases and injuries including muscular dystrophy, cerebral palsy, exercise-related injuries, rotator cuff tears, and age-related muscle loss (1).
A new form of 3D imaging of muscles has allowed researchers to "see" inside muscle and trace long cables made up of a protein called collagen. Collagen cables are one culprit behind muscular diseases and injuries, so targeting them could provide treatments.
That's according to new research from a team at UC San Diego and the Rehabilitation Institute of Chicago (RIC) led by Dr. Richard Lieber, currently Chief Scientific Officer at RIC and published in The Journal of Physiology.
Muscular conditions, whether hereditary, exercise-induced, or due to normal aging, can result in stiff, dysfunctional muscles due to changes called fibrosis. Fibrosis is a roadblock to muscle recovery, and can result in muscle pain, weakness, limited range of motion, or require surgery to treat it.
Researchers used a mouse model of skeletal muscle fibrosis to investigate the structure and function of collagen. They visualized collagen with conventional 2D and a newly developed method of 3D electron microscopy, mechanically measured muscle stiffness, and quantified the collagen producing cells.
Dr. Allison Gillies, first author of the study, said:
"The first time we looked at the 3D imaging results we were surprised--the collagen structures that we saw did not fit the textbook definition of muscle."
Collagen had not been previously known to form long chains in muscle. Researchers had seen collagen outside muscle cells, but had not determined the level of organization that could only be visualized by 3D microscopy.
When muscles become fibrotic, the number of cables and cells that produce collagen both increase. These collagen cables and the cells that produce collagen are thus two enticing targets for treating muscle disease and injury.
Commenting on the study, senior author, Dr. Lieber said:
"Reducing the amount of collagen cables or collagen producing cells in fibrotic muscle may improve muscle function and reduce pain, even obviating the need for corrective surgery."
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Notes for Editors
1. Muscular dystrophy- Muscular Dystrophy UK, http://www.musculardystrophyuk.org
Cerebral palsy- http://www.cerebralpalsy.org.uk
Rotator cuff tear- UK Census (http://www.ons.gov.uk); Yamaguchi K, Ditsios K, Middleton WD et al 2006. The demographic and morphological features of rotator cuff disease. A comparison of asymptomatic and symptomatic shoulders. Journal of Bone & Joint Surgery (Am) 88(8):1699-704; and Tempelhof S, Rupp S, Seil R 1999. Age-related prevalence of rotator cuff tears in asymptomatic shoulders. Journal of Shoulder & Elbow Surgery 8(4):296-9.
Sarcopenia- UK Census (http://www.ons.gov.uk) and Patel HP, Syddall HE, Jameson K et al 2013. Prevalence of sarcopenia in community-dwelling older people in the UK using the European Working Group on Sarcopenia in Older People (EWGSOP) definition: findings from the Hertfordshire Cohort Study (HCS). Age & Ageing 42(3):378-84.
Exercise related injuries- Nicholl JP, Coleman P, Williams BT 1991. Pilot study of the epidemiology of sports injuries and exercise-related morbidity. British Journal of Sports Medicine 25(1):61-6; and S Boyce and M Quigley 2004. Review of sports injuries presenting to an accident and emergency department. Emergency Medicine Journal 21(6):704-706.
2. Full paper title: High resolution three-dimensional reconstruction of fibrotic skeletal muscle extracellular matrix
3. The Journal of Physiology publishes advances in physiology that increase our understanding of how our bodies function in health and disease. http://jp.physoc.org
4. The Physiological Society brings together over 3,500 scientists from over 60 countries. The Society promotes physiology with the public and parliament alike. It supports physiologists by organizing world-class conferences and offering grants for research and also publishes the latest developments in the field in its three leading scientific journals, The Journal of Physiology, Experimental Physiology and Physiological Reports. http://www.physoc.org
5. The research was performed at UC San Diego and the Rehabilitation Institute of Chicago under Dr. Richard Lieber in collaboration with the National Center for Microscopy and Imaging Research led by Dr. Mark Ellisman.
6. Limitations
a. While the mouse model is genetically similar to human desminopathy, it differs from human muscle fibrosis because the mice do not show the variety of disease severity seen in humans.
b. Three-dimensional reconstructions sampled a small volume of fibrotic muscle due to the technical limitations of this imaging method. There may be additional changes in muscle that the researchers have not seen yet.
c. Collagen is one of many proteins in the extracellular matrix. The researchers studied it because it's the most abundant. There may be other proteins altered with fibrosis that may affect muscle stiffness and function.
Contacts:
The Physiological Society:
Julia Turan, Communications Manager
+44 (0)20 7269 5727, jturan@physoc.org
Richard L. Lieber, PhD
Senior Vice President & Chief Scientific Officer ?Rehabilitation Institute of Chicago
345 East Superior St, Chicago, IL 60611
rlieber@ric.org
Direct: 312-238-6260
Fax: 312-238-7554
Journal
The Journal of Physiology