{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T06:33:48Z","timestamp":1791614028272,"version":"4.3.4"},"reference-count":39,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2021,3,31]],"date-time":"2021-03-31T00:00:00Z","timestamp":1617148800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Japan Society for the Promotion of Science (JSPS) Grant-in-Aid for Scientific Research (B)","award":["25282202"],"award-info":[{"award-number":["25282202"]}]},{"name":"Grant-in-Aid for JSPS Research Fellow","award":["11J04790"],"award-info":[{"award-number":["11J04790"]}]},{"name":"Intramural Research Grant for Neurological and Psychiatric Disorders of NCNP","award":["28-6"],"award-info":[{"award-number":["28-6"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/ijms22073627","type":"journal-article","created":{"date-parts":[[2021,3,31]],"date-time":"2021-03-31T05:57:18Z","timestamp":1617170238000},"page":"3627","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Periostin Is Required for the Maintenance of Muscle Fibers during Muscle Regeneration"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1884-8494","authenticated-orcid":false,"given":"Naoki","family":"Ito","sequence":"first","affiliation":[{"name":"Laboratory of Molecular Life Science, Institute of Biomedical Research and Innovation (IBRI), Foundation for Biomedical Research and Innovation at Kobe (FBRI), Kobe 650-0047, Japan"},{"name":"National Center of Neurology and Psychiatry, Department of Molecular Therapy, National Institute of Neuroscience, Tokyo 187-8502, Japan"},{"name":"Department of Biological Information, Tokyo Institute of Technology, Yokohama 226-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8458-6237","authenticated-orcid":false,"given":"Yuko","family":"Miyagoe-Suzuki","sequence":"additional","affiliation":[{"name":"National Center of Neurology and Psychiatry, Department of Molecular Therapy, National Institute of Neuroscience, Tokyo 187-8502, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shin\u2019ichi","family":"Takeda","sequence":"additional","affiliation":[{"name":"National Center of Neurology and Psychiatry, Department of Molecular Therapy, National Institute of Neuroscience, Tokyo 187-8502, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akira","family":"Kudo","sequence":"additional","affiliation":[{"name":"Department of Biological Information, Tokyo Institute of Technology, Yokohama 226-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,3,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3232","DOI":"10.1016\/j.yexcr.2008.08.008","article-title":"Suppression of macrophage functions impairs skeletal muscle regeneration with severe fibrosis","volume":"314","author":"Segawa","year":"2008","journal-title":"Exp. Cell Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1016\/j.stem.2018.10.006","article-title":"Orienting Muscle Stem Cells for Regeneration in Homeostasis, Aging, and Disease","volume":"23","author":"Feige","year":"2018","journal-title":"Cell Stem Cell"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1002\/dvdy.24379","article-title":"Extracellular matrix bioscaffolds in tissue remodeling and morphogenesis","volume":"245","author":"Swinehart","year":"2016","journal-title":"Dev. Dyn."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1042\/bj2940271","article-title":"Osteoblast-specific factor 2: Cloning of a putative bone adhesion protein with homology with the insect protein fasciclin I","volume":"294","author":"Takeshita","year":"1993","journal-title":"Biochem. J."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"4259","DOI":"10.1007\/s00018-017-2643-5","article-title":"Introductory review: Periostin\u2014Gene and protein structure","volume":"74","author":"Kudo","year":"2017","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1239","DOI":"10.1359\/jbmr.1999.14.7.1239","article-title":"Identification and Characterization of a Novel Protein, Periostin, with Restricted Expression to Periosteum and Periodontal Ligament and Increased Expression by Transforming Growth Factor \u03b2","volume":"14","author":"Horiuchi","year":"1999","journal-title":"J. Bone Miner. Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1369\/jhc.2008.951061","article-title":"Periostin Is Expressed in Pericryptal Fibroblasts and Cancer-associated Fibroblasts in the Colon","volume":"56","author":"Kikuchi","year":"2008","journal-title":"J. Histochem. Cytochem."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1084\/jem.20071297","article-title":"Periostin is essential for cardiac healingafter acute myocardial infarction","volume":"205","author":"Shimazaki","year":"2008","journal-title":"J. Exp. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1152\/physiolgenomics.00056.2003","article-title":"Transcriptional profiling and regulation of the extracellular matrix during muscle regeneration","volume":"14","author":"Goetsch","year":"2003","journal-title":"Physiol. Genom."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"10978","DOI":"10.1073\/pnas.1204708109","article-title":"Deletion of periostin reduces muscular dystrophy and fibrosis in mice by modulating the transforming growth factor- pathway","volume":"109","author":"Lorts","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"3201","DOI":"10.1007\/s00018-011-0784-5","article-title":"Periostin in fibrillogenesis for tissue regeneration: Periostin actions inside and outside the cell","volume":"68","author":"Kudo","year":"2011","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"766","DOI":"10.1016\/j.bbrc.2006.02.016","article-title":"Periostin is an extracellular matrix protein required for eruption of incisors in mice","volume":"342","author":"Kii","year":"2006","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1002\/jcb.21224","article-title":"Periostin regulates collagen fibrillogenesis and the biomechanical properties of connective tissues","volume":"101","author":"Norris","year":"2007","journal-title":"J. Cell. Biochem."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1016\/j.jaci.2006.02.046","article-title":"Periostin: A novel component of subepithelial fibrosis of bronchial asthma downstream of IL-4 and IL-13 signals","volume":"118","author":"Takayama","year":"2006","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2028","DOI":"10.1074\/jbc.M109.051961","article-title":"Incorporation of Tenascin-C into the Extracellular Matrix by Periostin Underlies an Extracellular Meshwork Architecture","volume":"285","author":"Kii","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2082","DOI":"10.1038\/sj.onc.1210009","article-title":"Periostin promotes invasiveness and resistance of pancreatic cancer cells to hypoxia-induced cell death: Role of the \u03b24 integrin and the PI3k pathway","volume":"26","author":"Baril","year":"2006","journal-title":"Oncogene"},{"key":"ref_17","first-page":"5358","article-title":"Periostin secreted by epithelial ovarian carcinoma is a ligand for \u03b1V\u03b23 and \u03b1V\u03b25 integrins and promotes cell motility","volume":"62","author":"Gillan","year":"2002","journal-title":"Cancer Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1396","DOI":"10.1038\/sj.bjc.6603431","article-title":"Periostin is frequently overexpressed and enhances invasion and angiogenesis in oral cancer","volume":"95","author":"Siriwardena","year":"2006","journal-title":"Br. J. Cancer"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"e108","DOI":"10.2106\/JBJS.17.01230","article-title":"Periostin Promotes Fibroblast Migration and Inhibits Muscle Repair After Skeletal Muscle Injury","volume":"100","author":"Hara","year":"2018","journal-title":"J. Bone Jt. Surg. Am. Vol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1016\/j.ydbio.2003.12.007","article-title":"Zebrafish periostin is required for the adhesion of muscle fiber bundles to the myoseptum and for the differentiation of muscle fibers","volume":"267","author":"Kudo","year":"2004","journal-title":"Dev. Biol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"781","DOI":"10.2353\/ajpath.2008.070902","article-title":"Muscle CD31(\u2212) CD45(\u2212) Side Population Cells Promote Muscle Regeneration by Stimulating Proliferation and Migration of Myoblasts","volume":"173","author":"Motohashi","year":"2008","journal-title":"Am. J. Pathol."},{"key":"ref_22","first-page":"1","article-title":"Periosteum contains skeletal stem cells with high bone regenerative potential controlled by Periostin","volume":"9","author":"Julien","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Hardy, D., Besnard, A., Latil, M., Jouvion, G., Briand, D., Th\u00e9penier, C., Pascal, Q., Guguin, A., Gayraud-Morel, B., and Cavaillon, J.-M. (2016). Comparative Study of Injury Models for Studying Muscle Regeneration in Mice. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0147198"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1189","DOI":"10.1073\/pnas.81.4.1189","article-title":"X chromosome-linked muscular dystrophy (mdx) in the mouse","volume":"81","author":"Bulfield","year":"1984","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2414","DOI":"10.2353\/ajpath.2010.090887","article-title":"Genetic Background Affects Properties of Satellite Cells and mdx Phenotypes","volume":"176","author":"Fukada","year":"2010","journal-title":"Am. J. Pathol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1016\/S0896-6273(00)80894-6","article-title":"Maturation and Maintenance of the Neuromuscular Synapse","volume":"25","author":"Grady","year":"2000","journal-title":"Neuron"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1002\/aja.1001800303","article-title":"Distribution of connective tissue proteins in chick muscle spindles as revealed by monoclonal antibodies: A unique distribution of brachionectin\/tenascin","volume":"180","author":"Maier","year":"1987","journal-title":"Am. J. Anat."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1545","DOI":"10.2353\/ajpath.2009.090052","article-title":"Myotendinous Junction Defects and Reduced Force Transmission in Mice that Lack \u03b17 Integrin and Utrophin","volume":"175","author":"Welser","year":"2009","journal-title":"Am. J. Pathol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2578","DOI":"10.1172\/JCI98857","article-title":"Macrophage-lineage TRAP+ cells recruit periosteum-derived cells for periosteal osteogenesis and regeneration","volume":"129","author":"Gao","year":"2019","journal-title":"J. Clin. Investig."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"3992","DOI":"10.1128\/MCB.24.9.3992-4003.2004","article-title":"Acquired Expression of Periostin by Human Breast Cancers Promotes Tumor Angiogenesis through Up-Regulation of Vascular Endothelial Growth Factor Receptor 2 Expression","volume":"24","author":"Shao","year":"2004","journal-title":"Mol. Cell. Biol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"40148","DOI":"10.18632\/oncotarget.9512","article-title":"Periostin promotes tumor angiogenesis in pancreatic cancer via Erk\/VEGF signaling","volume":"7","author":"Liu","year":"2016","journal-title":"Oncotarget"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2183","DOI":"10.1016\/j.biocel.2008.02.017","article-title":"Matrix metalloproteinase-2 mediates stretch-induced activation of skeletal muscle satellite cells in a nitric oxide-dependent manner","volume":"40","author":"Yamada","year":"2008","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1016\/j.jconrel.2004.07.008","article-title":"Type I collagen can function as a reservoir of basic fibroblast growth factor","volume":"99","author":"Kanematsu","year":"2004","journal-title":"J. Control. Release"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"337","DOI":"10.4161\/cam.3.4.9338","article-title":"Role of matrix metalloproteinases in skeletal muscle","volume":"3","author":"Chen","year":"2009","journal-title":"Cell Adhes. Migr."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1186\/2044-5040-1-13","article-title":"\u03b4-Sarcoglycan-deficient muscular dystrophy: From discovery to therapeutic approaches","volume":"1","author":"Blain","year":"2011","journal-title":"Skelet. Muscle"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2169","DOI":"10.1074\/mcp.M116.059188","article-title":"Molecular Signatures of Membrane Protein Complexes Underlying Muscular Dystrophy","volume":"15","author":"Turk","year":"2016","journal-title":"Mol. Cell. Proteom."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1038\/nm.3019","article-title":"Activation of calcium signaling through Trpv1 by nNOS and peroxynitrite as a key trigger of skeletal muscle hypertrophy","volume":"19","author":"Ito","year":"2013","journal-title":"Nat. Med."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Ito, N., Ruegg, U.T., and Takeda, S. (2018). ATP-Induced Increase in Intracellular Calcium Levels and Subsequent Activation of mTOR as Regulators of Skeletal Muscle Hypertrophy. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19092804"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41598-017-08232-2","article-title":"Direct reprogramming of fibroblasts into skeletal muscle progenitor cells by transcription factors enriched in undifferentiated subpopulation of satellite cells","volume":"7","author":"Ito","year":"2017","journal-title":"Sci. Rep."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/7\/3627\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T13:33:15Z","timestamp":1760362395000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/7\/3627"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,31]]},"references-count":39,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2021,4]]}},"alternative-id":["ijms22073627"],"URL":"https:\/\/doi.org\/10.3390\/ijms22073627","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,3,31]]}}}