Research Article| Volume 11, ISSUE 4, P360-369, May 2001

Regulation of α7 integrin by mechanical stress during skeletal muscle regeneration


      The continuity of the tendon–myofibre–tendon units disrupted by shearing injury must be re-established during regeneration. We have previously demonstrated in freely moving rats that transected myofibres reinforce their lateral integrin-mediated adhesion, with the maximum around days 5–7. After day 14, most integrin molecules are redistributed to the newly formed myotendinous junctions, by which the ends of regenerating myofibres attach to the scar between the stumps. Here, we analyzed the effects of mechanical stress (free and forced mobilization vs. immobilization and denervation separately and in combination) on the expression of α7 integrin and merosin in regenerating myofibres using quantitative in situ hybridization and immunohistochemistry. In all groups, α7 integrin expression was upregulated at mRNA level, whereas increased protein accumulation in lateral sarcolemma occurred only in the mobilized groups. The accumulation of merosin was not affected by the stress level. The results demonstrate that active mechanical stress reinforces early lateral integrin-mediated adhesion; molecules may at the same time mediate signals from matrix to cells for adaptation to the altered biomechanical status.


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Neuromuscular Disorders
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Giancotti F.G
        • Ruoslahti E
        Integrin signaling.
        Science. 1999; 285: 1028-1032
        • Hynes R.O
        Integrins: a family of cell surface receptors.
        Cell. 1987; 48: 549-554
        • Meredith J.E
        • Winitz S
        • Lewis J.M
        • et al.
        The regulation of growth and intracellular signaling by integrins.
        Endocr Rev. 1996; 17: 207-220
        • Brown R.H
        Dystrophin-associated proteins and the muscular dystrophies: a glossary.
        Brain Pathol. 1996; 6: 19-24
        • Ervasti J.M
        • Campbell K.P
        Dystrophin and the membrane skeleton.
        Curr Opin Cell Biol. 1993; 5: 82-87
        • Sunada Y
        • Campbell K.P
        Dystrophin–glycoprotein complex: molecular organization and critical roles in skeletal muscle.
        Curr Opin Neurol. 1995; 8: 379-384
        • Song W.K
        • Wang W
        • Foster R.F
        • Bielser D.A
        • Kaufman S.J
        H36-α7 is a novel integrin alpha chain that is developmentally regulated during skeletal myogenesis.
        J Cell Biol. 1993; 117: 643-657
        • Otey C.A
        • Pavalko F.M
        • Burridge K
        An interaction between α-actinin and the β1 integrin subunit in vitro.
        J Cell Biol. 1990; 111: 721-729
        • Horwitz A
        • Duggan K
        • Buck C
        • Beckerle M.C
        • Burridge K
        Interaction of plasma membrane fibronectin receptor with talin – a transmembrane linkage.
        Nature. 1986; 320: 531-533
        • Yao C
        • Ziober B.L
        • Squillace R.M
        • Kramer R.H
        α7 integrin mediates cell adhesion and migration on specific laminin isoforms.
        J Biol Chem. 1996; 271: 15598-25603
        • von der Mark H
        • Dürr J
        • Sonnenberg A
        • von der Mark K
        • Deutzmann R
        • Goodman S.L
        Skeletal myoblasts utilize a novel β1-series integrin and not α6β1 for binding to the E8 and T8 fragments of laminin.
        J Biol Chem. 1991; 266: 23593-23601
        • Engvall E
        • Earwicker D
        • Haaparanta T
        • Ruoslahti E
        • Sanes J.R
        Distribution and isolation of four laminin variants: tissue restricted distribution of heterotrimers assembled from five different subunits.
        Cell Regulation. 1990; 1: 731-740
        • Engvall E
        Laminin variants: why, where and when?.
        Kidney Int. 1993; 43: 2-6
        • Bao Z.Z
        • Lakonishok M
        • Kaufman S
        • Horwitz A.F
        α7β1 integrin is a component of the myotendinous junction on skeletal muscle.
        J Cell Sci. 1993; 106: 579-590
        • Tidball J.G
        • Daniel T.L
        Myotendinous junctions of tonic muscle cells: structure and loading.
        Cell Tissue Res. 1986; 245: 315-322
        • Tidball J.G
        Force transmission across muscle membrane.
        J Biomech. 1991; 24(Suppl 1): 43-52
        • Kääriäinen M
        • Kääriäinen J
        • Järvinen T.L.N
        • et al.
        Integrin and dystrophin associated adhesion protein complexes during regeneration of shearing-type muscle injury.
        Neuromusc Disord. 2000; 10: 121-132
        • Chiquet M
        Regulation of extracellular matrix gene expression by mechanical stress.
        Matrix Biol. 1999; 18: 417-426
        • Kääriäinen M
        • Kääriäinen J
        • Järvinen T.L.N
        • Sievänen H
        • Kalimo H
        • Järvinen M
        Correlation between biomechanical and structural changes during the regeneration after laceration injury of skeletal muscle.
        J Orthop Res. 1998; 16: 197-206
      1. Kononen J, Pelto-Huikko M. Recycling of tissue sections with a simple and sensitive mRNA in situ hybridization technique. TIGS Technical Tips Online:

        • Song W.K
        • Wang W
        • Foster R.F
        • Bielser D.A
        • Kaufman S.J
        H36-α7 is a novel integrin alpha chain that is developmentally regulated during skeletal myogenesis.
        J Cell Biol. 1992; 117: 643-657
        • Collo G
        • Starr L
        • Quaranta V
        A new isoform of the laminin receptor integrin α7β1 is developmentally regulated in skeletal muscle.
        J Biol Chem. 1993; 268: 19019-19024
        • Hurme T
        • Kalimo H
        • Lehto M
        • Järvinen M
        Healing of skeletal muscle injury: an ultrastructural and immunohistochemical study.
        Med Sci Sports Exerc. 1991; 23: 801-810
        • Järvinen M
        Healing of a crush injury in rat striated muscle. 2. A histological study of the effect of early mobilization and immobilization on the repair process.
        Acta Pathol Microbiol Scand. 1975; A83: 269-282
        • Järvinen M.J
        • Lehto M.U
        The effects of early mobilization and immobilization on the healing process following muscle injuries.
        Sports Med. 1993; 15: 78-89
        • Kalimo H
        • Rantanen J
        • Järvinen M
        Muscle injuries in sports.
        in: Järvinen M Baillière's clinical orthopaedics: soft tissue injuries in sports, Volume 2 Number 1. W.B. Saunders, Philadelphia, PA1997: 1-24
        • Järvinen M
        Healing of crush injury in rat striated muscle. 4. Effect of early mobilization and immobilization on the tensile properties of gastrocnemius muscle.
        Acta Chir Scand. 1976; 142: 47-56
        • Kannus P
        • Jozsa L
        • Kvist M
        • Järvinen T
        • Järvinen M
        Effects of immobilization and subsequent low- and high-intensity exercise on morphology of rat calf muscles.
        Scand J Med Sci Sports. 1998; 8: 160-171
        • Hodges B.L
        • Hayashi Y.K
        • Nonaka I
        • Wang W
        • Arahata K
        • Kaufman S.J
        Altered expression of the alpha7beta1 integrin in human and murine muscular dystrophies.
        J Cell Sci. 1997; 110: 2873-2881
        • Oluwole B.O
        • Du W
        • Mills I
        • Sumpio B.E
        Gene regulation by mechanical forces.
        Endothelium. 1997; 5: 85-93
        • Tang D
        • Mehta D
        • Gunst S.J
        Mechanosensitive tyrosine phosphorylation of paxillin and focal adhesion kinase in tracheal smooth muscle.
        Am J Physiol. 1999; 276: 250-258
        • Vaittinen S
        • Lukka R
        • Sahlgren C
        • et al.
        Specific and innervation-regulated expression of the intermediate filament protein nestin at neuromuscular and myotendinous junctions in skeletal muscle.
        Am J Pathol. 1999; 154: 591-600
        • Felsenfeld D.P
        • Choquet D
        • Sheetz M.P
        Ligand binding regulates the directed movement of β1 integrins on fibroblasts.
        Nature. 1996; 383: 438-440