Reduced skeletal muscle satellite cell number alters muscle morphology after chronic stretch but allows limited serial sarcomere addition

Matthew C. Kinney; Sudarshan Dayanidhi; Peter B. Dykstra; John J. McCarthy; Charlotte A. Peterson; Richard L. Lieber

doi:10.1002/mus.25227

Reduced skeletal muscle satellite cell number alters muscle morphology after chronic stretch but allows limited serial sarcomere addition

Matthew C. Kinney, Sudarshan Dayanidhi, Peter B. Dykstra, John J. McCarthy, Charlotte A. Peterson, Richard L. Lieber^*

^*Corresponding author for this work

Physical Medicine and Rehabilitation

Research output: Contribution to journal › Article › peer-review

40 Scopus citations

Abstract

Introduction: Muscles add sarcomeres in response to stretch, presumably to maintain optimal sarcomere length. Clinical evidence from patients with cerebral palsy, who have both decreased serial sarcomere number and reduced satellite cells (SCs), suggests a hypothesis that SCs may be involved in sarcomere addition. Methods: A transgenic Pax7-DTA mouse model underwent conditional SC depletion, and their soleii were then stretch-immobilized to assess the capacity for sarcomere addition. Muscle architecture, morphology, and extracellular matrix (ECM) changes were also evaluated. Results: Mice in the SC-reduced group achieved normal serial sarcomere addition in response to stretch. However, muscle fiber cross-sectional area was significantly smaller and was associated with hypertrophic ECM changes, consistent with fibrosis. Conclusions: While a reduced SC population does not hinder serial sarcomere addition, SCs play a role in muscle adaptation to chronic stretch that involves maintenance of both fiber cross-sectional area and ECM structure. Muscle Nerve 55: 384–392, 2017.

Original language	English (US)
Pages (from-to)	384-392
Number of pages	9
Journal	Muscle and Nerve
Volume	55
Issue number	3
DOIs	https://doi.org/10.1002/mus.25227
State	Published - Mar 1 2017

Funding

None of the authors have any conflict of interest or financial disclosures related to this work. We appreciate the assistance of Dr. Simon Schenk with mouse treatment, Mary Esparza with muscle harvesting, and Dr. Gretchen Meyer with flow cytometry methods. The authors acknowledge NIH grants P30AR061303 and HD050837 and Department of Veterans Affairs grant A9028-R for support. This research was also aided by a grant from the Orthopaedic Research and Education Foundation, with Funding Provided by Depuy Synthes Joint Reconstruction.

Keywords

cerebral palsy
chronic stretch
fibrosis
sarcomere addition
satellite cells
skeletal muscles

ASJC Scopus subject areas

Physiology
Clinical Neurology
Cellular and Molecular Neuroscience
Physiology (medical)

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title = "Reduced skeletal muscle satellite cell number alters muscle morphology after chronic stretch but allows limited serial sarcomere addition",

abstract = "Introduction: Muscles add sarcomeres in response to stretch, presumably to maintain optimal sarcomere length. Clinical evidence from patients with cerebral palsy, who have both decreased serial sarcomere number and reduced satellite cells (SCs), suggests a hypothesis that SCs may be involved in sarcomere addition. Methods: A transgenic Pax7-DTA mouse model underwent conditional SC depletion, and their soleii were then stretch-immobilized to assess the capacity for sarcomere addition. Muscle architecture, morphology, and extracellular matrix (ECM) changes were also evaluated. Results: Mice in the SC-reduced group achieved normal serial sarcomere addition in response to stretch. However, muscle fiber cross-sectional area was significantly smaller and was associated with hypertrophic ECM changes, consistent with fibrosis. Conclusions: While a reduced SC population does not hinder serial sarcomere addition, SCs play a role in muscle adaptation to chronic stretch that involves maintenance of both fiber cross-sectional area and ECM structure. Muscle Nerve 55: 384–392, 2017.",

keywords = "cerebral palsy, chronic stretch, fibrosis, sarcomere addition, satellite cells, skeletal muscles",

author = "Kinney, {Matthew C.} and Sudarshan Dayanidhi and Dykstra, {Peter B.} and McCarthy, {John J.} and Peterson, {Charlotte A.} and Lieber, {Richard L.}",

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doi = "10.1002/mus.25227",

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AU - Dayanidhi, Sudarshan

AU - Dykstra, Peter B.

AU - McCarthy, John J.

AU - Peterson, Charlotte A.

AU - Lieber, Richard L.

PY - 2017/3/1

Y1 - 2017/3/1

N2 - Introduction: Muscles add sarcomeres in response to stretch, presumably to maintain optimal sarcomere length. Clinical evidence from patients with cerebral palsy, who have both decreased serial sarcomere number and reduced satellite cells (SCs), suggests a hypothesis that SCs may be involved in sarcomere addition. Methods: A transgenic Pax7-DTA mouse model underwent conditional SC depletion, and their soleii were then stretch-immobilized to assess the capacity for sarcomere addition. Muscle architecture, morphology, and extracellular matrix (ECM) changes were also evaluated. Results: Mice in the SC-reduced group achieved normal serial sarcomere addition in response to stretch. However, muscle fiber cross-sectional area was significantly smaller and was associated with hypertrophic ECM changes, consistent with fibrosis. Conclusions: While a reduced SC population does not hinder serial sarcomere addition, SCs play a role in muscle adaptation to chronic stretch that involves maintenance of both fiber cross-sectional area and ECM structure. Muscle Nerve 55: 384–392, 2017.

AB - Introduction: Muscles add sarcomeres in response to stretch, presumably to maintain optimal sarcomere length. Clinical evidence from patients with cerebral palsy, who have both decreased serial sarcomere number and reduced satellite cells (SCs), suggests a hypothesis that SCs may be involved in sarcomere addition. Methods: A transgenic Pax7-DTA mouse model underwent conditional SC depletion, and their soleii were then stretch-immobilized to assess the capacity for sarcomere addition. Muscle architecture, morphology, and extracellular matrix (ECM) changes were also evaluated. Results: Mice in the SC-reduced group achieved normal serial sarcomere addition in response to stretch. However, muscle fiber cross-sectional area was significantly smaller and was associated with hypertrophic ECM changes, consistent with fibrosis. Conclusions: While a reduced SC population does not hinder serial sarcomere addition, SCs play a role in muscle adaptation to chronic stretch that involves maintenance of both fiber cross-sectional area and ECM structure. Muscle Nerve 55: 384–392, 2017.

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Reduced skeletal muscle satellite cell number alters muscle morphology after chronic stretch but allows limited serial sarcomere addition

Abstract

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