Origin of cells that contribute to heterotopic ossification in skeletal muscle

2013 Fiscal Year Final Research Report

• Project/Area Number: 24659687
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Single-year Grants
• Research Field: Orthopaedic surgery
• Research Institution: Fujita Health University
• Principal Investigator: UEZUMI Akiyoshi 藤田保健衛生大学, 総合医科学研究所, 助教 (60434594)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Keywords: 異所性骨化 / 骨格筋 / 間葉系前駆細胞

Research Abstract

Fibrodysplasia ossificans progressiva (FOP) is a severely disabling heritable disorder of connective tissue characterized by progressive extraskeletal ossification in skeletal muscle. Mutation of the ALK-2 gene, a BMP type I receptor, was identified in FOP patients and has been shown to contribute to the pathogenesis of FOP. Skeletal muscle contains two types of progenitor cells: satellite cells and mesenchymal progenitor cells (MPC). In this study, we investigated possible involvement of these progenitors in the pathogenesis of FOP. We established techniques for isolating and culturing satellite cells and MPC from human skeletal muscle. Human MPC showed much higher osteogenic potential than human satellite cells and MPC transduced with mutant ALK-2 contributed heterotopic ossification when transplanted into immunodeficient mice. Our results strongly suggest that MPC represents best possible candidate for cellular origin of heterotopic ossification in skeletal muscle.

Research Products

• [Journal Article] Identification and characterization of PDGFRα+ mesenchymal progenitors in human skeletal muscle (2014)
  • Author(s): Uezumi A, Fukada S, Yamamoto N, Ikemoto-Uezumi M, Nakatani M, Morita M, Yamaguchi A, Yamada H, Nishino I, Hamada Y, Tsuchida K
  • Journal Title: Cell Death Dis Volume: 5 Pages: e1186
  • DOI: 10.1038/cddis.2014.161
  • Peer Reviewed
• [Journal Article] Roles of nonmyogenic mesenchymal progenitors in pathogenesis and regeneration of skeletal muscle (2014)
  • Author(s): Uezumi A, Ikemoto-Uezumi M, Tsuchida K
  • Journal Title: Front Physiol Volume: 5 Pages: 68
  • URL: http://journal.frontiersin.org/Journal/10.3389/fphys.2014.00068/abstract
  • Peer Reviewed
• [Journal Article] Osteogenic differentiation capacity of human skeletal muscle-derived progenitor cells (2013)
  • Author(s): Oishi T, Uezumi A, Kanaji A, Yamamoto N, Yamaguchi A, Yamada H, Tsuchida K
  • Journal Title: PLoS One Volume: 8(2) Pages: e56641
  • DOI: 10.1371/journal.pone.0056641
  • Peer Reviewed
• [Presentation] 霜降りの起源となる細胞の表現型を制御するメカニズム (2014)
  • Author(s): 上住聡芳
  • Organizer: 第118回日本畜産学会
  • Place of Presentation: つくば
  • Year and Date: 2014-03-26
• [Presentation] 骨格筋内在性間葉系前駆細胞による筋再生促進機構の解析 (2014)
  • Author(s): 上住聡芳
  • Organizer: 第13回日本再生医療学会総会
  • Place of Presentation: 京都
  • Year and Date: 2014-03-04
• [Presentation] Roles for nonmyogenic mesenchymal progenitors in skeletal muscle regeneration (2012)
  • Author(s): Uezumi A
  • Organizer: 9th Japanese-French Symposium for'muscular dystrophy'
  • Place of Presentation: 東京
  • Year and Date: 2012-09-07
• [Presentation] Roles for nonmyogenic mesenchymal progenitors in skeletal muscle regeneration (2012)
  • Author(s): Uezumi A
  • Organizer: FASEB Science Research Conference : Skeletal Muscle Satellite and Stem Cells
  • Place of Presentation: Lucca, Italy
  • Year and Date: 2012-08-15
• [Book] 整形・災害外科 (2013)
  • Author(s): 上住聡芳, 他
  • Total Pages: 695
  • Publisher: 金原出版
• [Book] 生体の科学 (2013)
  • Author(s): 上住聡芳, 他
  • Total Pages: 192
  • Publisher: 医学書院