Periostin Is Required for the Maintenance of Muscle Fibers during Muscle Regeneration.

Naoki Ito,Akira Kudo,Yuko Miyagoe-Suzuki,Shin’Ichi Takeda

doi:10.3390/ijms22073627

Abstract

Skeletal muscle regeneration is a well-organized process that requires remodeling of the extracellular matrix (ECM). In this study, we revealed the protective role of periostin, a matricellular protein that binds to several ECM proteins during muscle regeneration. In intact muscle, periostin was localized at the neuromuscular junction, muscle spindle, and myotendinous junction, which are connection sites between muscle fibers and nerves or tendons. During muscle regeneration, periostin exhibited robustly increased expression and localization at the interstitial space. Periostin-null mice showed decreased muscle weight due to the loss of muscle fibers during repeated muscle regeneration. Cultured muscle progenitor cells from periostin-null mice showed no deficiencies in their proliferation, differentiation, and the expression of Pax7, MyoD, and myogenin, suggesting that the loss of muscle fibers in periostin-null mice was not due to the impaired function of muscle stem/progenitor cells. Periostin-null mice displayed a decreased number of CD31-positive blood vessels during muscle regeneration, suggesting that the decreased nutritional supply from blood vessels was the cause of muscle fiber loss in periostin-null mice. These results highlight the novel role of periostin in maintaining muscle mass during muscle regeneration.

Highlights

Skeletal muscle has a high regenerative ability
We found that CD31-positive blood interstitial space and some CD31 signals were surrounded by periostin during muscle regeneration (Figure 3c), we counted the number of CD31-positive blood vessels after revsuegspslosigegeseasnlstsieotfedfiwcdlpayeentrirhtenilaoydstsuitdlgiconeniscncsirgfiaeouacmfsasepeunddsetclraiylineoddsrpeteeceigncrreeironcaesaseateursianesitn-edinodmuninalu.lWsdpmceeleiecrcfriefoeoibua(sFesntriiedgnniu-tnunhrmeaumtl4bluCfe,smDrgc)d3li.ecu1Te-rfiphibn(eoFegssierigrtneiruvpeureseemuablt4lbteosfedo,rgsdmu)d.vguuegTsrsecihsnsleetegelssrdreewegtrpheeeneraseat-uteltds muesrcalteiorne,gpeonsesriabtliyodnu, pe otosstihbelydidmuienitsohtehdenduitmriitnioinshaledsunpuptlryitfiroonmalbsluoopdplvyesfrsoelms. blood vessels
Periostin was localized at the neuromuscular junction (NMJ), muscle spindle, and myotendinous junction (Figure 1), which are connection sites between skeletal muscle fibers and nerves or tendons

Summary

Introduction

Skeletal muscle has a high regenerative ability. When skeletal muscle is damaged by external factors, inflammatory cells such as monocytes and macrophages infiltrate and phagocytose necrotic fibers [1]. Skeletal muscle regeneration is a highly organized process including activation, proliferation, and differentiation of muscle satellite cells, which are tissue-specific stem cells in skeletal muscle [2]. In parallel with the removal of necrotic fibers by inflammatory cells, satellite cells are activated to become myoblasts, which proliferate, fuse with each other or existing muscle fibers, and form a myotube, thereby regenerating myofibers. These processes are accompanied by remodeling of the extracellular matrix (ECM), which surrounds skeletal muscle fibers [3]. As the muscle grows or regenerates, ECM is repeatedly degraded and reconstructed, which enables efficient cell proliferation and migration and maintains tissue strength

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