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@ARTICLE{Ggele:902164,
      author       = {Gögele, Clemens and Hoffmann, Christina and Konrad, Jens
                      and Merkel, Rudolf and Schwarz, Silke and Tohidnezhad,
                      Mersedeh and Hoffmann, Bernd and Schulze-Tanzil, Gundula
                      Gesine},
      title        = {{C}yclically stretched {ACL} fibroblasts emigrating from
                      spheroids adapt their cytoskeleton and ligament-related
                      expression profile},
      journal      = {Cell $\&$ tissue research},
      volume       = {384},
      number       = {3},
      issn         = {1432-0878},
      address      = {Heidelberg},
      publisher    = {Springer},
      reportid     = {FZJ-2021-04073},
      pages        = {675 - 690},
      year         = {2021},
      abstract     = {Mechanical stress of ligaments varies; hence, ligament
                      fibroblasts must adapt their expression profile to novel
                      mechanomilieus to ensure tissue resilience. Activation of
                      the mechanoreceptors leads to a specific signal
                      transduction, the so-called mechanotransduction. However,
                      with regard to their natural three-dimensional (3D)
                      microenvironment cell reaction to mechanical stimuli during
                      emigrating from a 3D spheroid culture is still unclear. This
                      study aims to provide a deeper understanding of the reaction
                      profile of anterior cruciate ligament (ACL)-derived
                      fibroblasts exposed to cyclic uniaxial strain in
                      two-dimensional (2D) monolayer culture and during emigration
                      from 3D spheroids with respect to cell survival, cell and
                      cytoskeletal orientation, distribution, and expression
                      profile. Monolayers and spheroids were cultured in
                      crosslinked polydimethyl siloxane (PDMS) elastomeric
                      chambers and uniaxially stretched $(14\%$ at 0.3 Hz) for 48
                      h. Cell vitality, their distribution, nuclear shape, stress
                      fiber orientation, focal adhesions, proliferation,
                      expression of ECM components such as sulfated
                      glycosaminoglycans, collagen type I, decorin, tenascin C and
                      cell–cell communication-related gap junctional connexin
                      (CXN) 43, tendon-related markers Mohawk and tenomodulin
                      (myodulin) were analyzed. In contrast to unstretched cells,
                      stretched fibroblasts showed elongation of stress fibers,
                      cell and cytoskeletal alignment perpendicular to strain
                      direction, less rounded cell nuclei, increased numbers of
                      focal adhesions, proliferation, amplified CXN43, and main
                      ECM component expression in both cultures. The applied
                      cyclic stretch protocol evoked an anabolic response and
                      enhanced tendon-related marker expression in ACL-derived
                      fibroblasts emigrating from 3D spheroids and seems also
                      promising to support in future tissue formation in ACL
                      scaffolds seeded in vitro with spheroids.},
      cin          = {IBI-2},
      ddc          = {610},
      cid          = {I:(DE-Juel1)IBI-2-20200312},
      pnm          = {5241 - Molecular Information Processing in Cellular Systems
                      (POF4-524)},
      pid          = {G:(DE-HGF)POF4-5241},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:33835257},
      UT           = {WOS:000638485300001},
      doi          = {10.1007/s00441-021-03416-9},
      url          = {https://juser.fz-juelich.de/record/902164},
}