The Structure and Role of Intramuscular Connective Tissue in Muscle Function

Purslow, Peter P.

doi:10.3389/fphys.2020.00495

Cited by 142 publications

(102 citation statements)

References 129 publications

(162 reference statements)

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“…Once thought of being a rather inert tissue component, it is now accepted that ECM is dynamic, responsive to environmental queues, and responsible for coordinating tissue responses. 2 ECM has important roles in maintaining muscle structure, 3 mechanotransduction, 4 and other forms of signaling. 5 , 6 There remains a need to explore changes in skeletal muscle ECM with age to understand age-related decline in muscle function.…”

Section: Introductionmentioning

confidence: 99%

A Novel Stable Isotope Approach Demonstrates Surprising Degree of Age-Related Decline in Skeletal Muscle Collagen Proteostasis

et al. 2021

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Age-related deterioration in turnover of collagen proteins accelerates extracellular matrix (ECM) fibrosis and hinders adaptation to external stimuli. This project sought to understand factors that increase skeletal muscle fibrosis with age by studying what we term the dynamic protein pool. We hypothesized that the dynamic protein pool size of muscle collagen decreases with age, thus indicating a decrease in proteostatic maintenance (i.e., ability to maintain proteostasis), and that failure to account for these changes impacts the interpretation of tracer-measured synthesis rates. We used deuterium oxide (D2O) labeling for up to 60 days in adult (6 months) and old (23 months) mice. The dynamic protein pool in adult skeletal muscle was 65% in tibialis anterior (TA), but only 28% in gastrocnemius (Gastroc). In aged muscle, the dynamic protein pool was further decreased to only 35% and 14% for TA and Gastroc, respectively. We showed that this loss in dynamic pool size was associated with increases in markers of fibrosis and decreased proteostatic maintenance. We demonstrate that aged muscle has higher rates of collagen protein synthesis and lower rates of collagen protein breakdown, which causes collagen accumulation. We further demonstrated that the normal assumption of complete protein renewal and the standard practice of taking a single sample with isotope labeling have profound impacts on interpretation of the genesis of fibrosis. Strategies to maintain muscle function with aging should focus on the dynamic protein pool with attention to methodological strategies to assess those changes.

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Section: Introductionmentioning

confidence: 99%

A Novel Stable Isotope Approach Demonstrates Surprising Degree of Age-Related Decline in Skeletal Muscle Collagen Proteostasis

et al. 2021

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“…Among the most affected tissues by fibrosis are the skin, liver, lungs, heart, kidney, eye, pancreas, intestine, brain, bone marrow, and skeletal muscles (Wynn and Ramalingam, 2012). Given the importance of scar formation in several tissues in pathology, disease, and aging (Brack and Rando, 2008;Grounds, 2008;Kharraz et al, 2014;Purslow, 2020), it is perhaps surprising that the biology of PDGFRα+ FAPs is not well understood yet.…”

Section: Fibro-adipogenic Progenitors As Pathological Drivers Of Muscmentioning

confidence: 99%

Evolving Roles of Muscle-Resident Fibro-Adipogenic Progenitors in Health, Regeneration, Neuromuscular Disorders, and Aging

2021

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Normal skeletal muscle functions are affected following trauma, chronic diseases, inherited neuromuscular disorders, aging, and cachexia, hampering the daily activities and quality of life of the affected patients. The maladaptive accumulation of fibrous intramuscular connective tissue and fat are hallmarks of multiple pathologies where chronic damage and inflammation are not resolved, leading to progressive muscle replacement and tissue degeneration. Muscle-resident fibro-adipogenic progenitors are adaptable stromal cells with multilineage potential. They are required for muscle homeostasis, neuromuscular integrity, and tissue regeneration. Fibro-adipogenic progenitors actively regulate and shape the extracellular matrix and exert immunomodulatory functions via cross-talk with multiple other residents and non-resident muscle cells. Remarkably, cumulative evidence shows that a significant proportion of activated fibroblasts, adipocytes, and bone-cartilage cells, found after muscle trauma and disease, descend from these enigmatic interstitial progenitors. Despite the profound impact of muscle disease on human health, the fibrous, fatty, and ectopic bone tissues’ origins are poorly understood. Here, we review the current knowledge of fibro-adipogenic progenitor function on muscle homeostatic integrity, regeneration, repair, and aging. We also discuss how scar-forming pathologies and disorders lead to dysregulations in their behavior and plasticity and how these stromal cells can control the onset and severity of muscle loss in disease. We finally explore the rationale of improving muscle regeneration by understanding and modulating fibro-adipogenic progenitors’ fate and behavior.

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“…The estimated percentage of elastic, with respect to collagen fibers, is approximately 15% [ 26 ]. Purslow et al demonstrated that the epimysium has the same organization as the aponeurotic fasciae which consist of two or three sublayers of connective tissue and they described three sublayers of the epimysium: the internal, the middle and the external sublayers [ 29 , 30 ].…”

Section: Microscopic Anatomy Of the Deep/muscular Fasciaementioning

confidence: 99%

A Closer Look at the Cellular and Molecular Components of the Deep/Muscular Fasciae

Fede

Pirri

Fan

et al. 2021

IJMS

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The fascia can be defined as a dynamic highly complex connective tissue network composed of different types of cells embedded in the extracellular matrix and nervous fibers: each component plays a specific role in the fascial system changing and responding to stimuli in different ways. This review intends to discuss the various components of the fascia and their specific roles; this will be carried out in the effort to shed light on the mechanisms by which they affect the entire network and all body systems. A clear understanding of fascial anatomy from a microscopic viewpoint can further elucidate its physiological and pathological characteristics and facilitate the identification of appropriate treatment strategies.

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The Structure and Role of Intramuscular Connective Tissue in Muscle Function

Cited by 142 publications

References 129 publications

A Novel Stable Isotope Approach Demonstrates Surprising Degree of Age-Related Decline in Skeletal Muscle Collagen Proteostasis

A Novel Stable Isotope Approach Demonstrates Surprising Degree of Age-Related Decline in Skeletal Muscle Collagen Proteostasis

Evolving Roles of Muscle-Resident Fibro-Adipogenic Progenitors in Health, Regeneration, Neuromuscular Disorders, and Aging

A Closer Look at the Cellular and Molecular Components of the Deep/Muscular Fasciae

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