@phdthesis{Kramer2021,
  author    = {Kramer, Lisa Sophie},
  title     = {Charakterisierung des Einflusses von Estrogenrezeptoren auf mechanoresponsive Reporter},
  doi       = {10.25972/OPUS-22270},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-222709},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2021},
  abstract  = {Osteoporose wird definiert als erworbene, generalisierte Skeletterkrankung, die durch eine verminderte Knochenfestigkeit und einen pathologischen Knochenverlust charakterisiert wird. Durch die St{\"o}rung der Mikroarchitektur kommt es zu strukturellen und funktionellen Defiziten im Sinne von Fragilit{\"a}tsfrakturen. Mechanische Stimulation erh{\"a}lt die Gewebemasse und stimuliert deren kontinuierliche Anpassung. {\"O}strogene spielen bei der Entwicklung, dem Wachstum und der Regeneration des Knochens eine bedeutende Rolle und wirken {\"u}ber Bindung an die {\"O}strogenrezeptoren ER und ER in bestimmten Zielgeweben. {\"O}strogenrezeptoren sind unver{\"a}ndert sehr geeignete Targets f{\"u}r die Entwicklung von Medikamenten im Rahmen der Osteoporosetherapie wie z.B. die selektiven {\"O}strogen-Rezeptor-Modulatoren (SERMs). Die molekulare Kl{\"a}rung der Einfl{\"u}sse von ER und ER ist unver{\"a}ndert von großer klinischer Bedeutung. Die Herstellung stabiler Zelllinien mit {\"U}berexpression von Reportergenkonstrukten und Rezeptoren kann dabei hilfreich sein. In dieser Arbeit wurde eine stabile Zelllinie mit {\"U}berexpression von ERβ etabliert, die unterschiedliche Wirkung von ER und ER wurden analysiert und die Effekte von zyklischer Dehnung auf Reportergenexpression unter der Kontrolle von mechanosensitiven responsiven Elementen wurden charakterisiert.},
  subject      = {{\"O}strogene},
  language  = {de}
}
@article{PereiraLipphausErginetal.2021,
  author    = {Pereira, Ana Rita and Lipphaus, Andreas and Ergin, Mert and Salehi, Sahar and Gehweiler, Dominic and Rudert, Maximilian and Hansmann, Jan and Herrmann, Marietta},
  title     = {Modeling of the Human Bone Environment: Mechanical Stimuli Guide Mesenchymal Stem Cell-Extracellular Matrix Interactions},
  series = {Materials},
  volume    = {14},
  journal   = {Materials},
  number    = {16},
  issn      = {1996-1944},
  doi       = {10.3390/ma14164431},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-245012},
  year      = {2021},
  abstract  = {In bone tissue engineering, the design of in vitro models able to recreate both the chemical composition, the structural architecture, and the overall mechanical environment of the native tissue is still often neglected. In this study, we apply a bioreactor system where human bone-marrow hMSCs are seeded in human femoral head-derived decellularized bone scaffolds and subjected to dynamic culture, i.e., shear stress induced by continuous cell culture medium perfusion at 1.7 mL/min flow rate and compressive stress by 10\% uniaxial load at 1 Hz for 1 h per day. In silico modeling revealed that continuous medium flow generates a mean shear stress of 8.5 mPa sensed by hMSCs seeded on 3D bone scaffolds. Experimentally, both dynamic conditions improved cell repopulation within the scaffold and boosted ECM production compared with static controls. Early response of hMSCs to mechanical stimuli comprises evident cell shape changes and stronger integrin-mediated adhesion to the matrix. Stress-induced Col6 and SPP1 gene expression suggests an early hMSC commitment towards osteogenic lineage independent of Runx2 signaling. This study provides a foundation for exploring the early effects of external mechanical stimuli on hMSC behavior in a biologically meaningful in vitro environment, opening new opportunities to study bone development, remodeling, and pathologies.},
  language  = {en}
}
@article{PaudelFusiSchmidt2021,
  author    = {Paudel, Rupesh and Fusi, Lorenza and Schmidt, Marc},
  title     = {The MEK5/ERK5 pathway in health and disease},
  series = {International Journal of Molecular Sciences},
  volume    = {22},
  journal   = {International Journal of Molecular Sciences},
  number    = {14},
  issn      = {1422-0067},
  doi       = {10.3390/ijms22147594},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-261638},
  year      = {2021},
  abstract  = {The MEK5/ERK5 mitogen-activated protein kinases (MAPK) cascade is a unique signaling module activated by both mitogens and stress stimuli, including cytokines, fluid shear stress, high osmolarity, and oxidative stress. Physiologically, it is mainly known as a mechanoreceptive pathway in the endothelium, where it transduces the various vasoprotective effects of laminar blood flow. However, it also maintains integrity in other tissues exposed to mechanical stress, including bone, cartilage, and muscle, where it exerts a key function as a survival and differentiation pathway. Beyond its diverse physiological roles, the MEK5/ERK5 pathway has also been implicated in various diseases, including cancer, where it has recently emerged as a major escape route, sustaining tumor cell survival and proliferation under drug stress. In addition, MEK5/ERK5 dysfunction may foster cardiovascular diseases such as atherosclerosis. Here, we highlight the importance of the MEK5/ERK5 pathway in health and disease, focusing on its role as a protective cascade in mechanical stress-exposed healthy tissues and its function as a therapy resistance pathway in cancers. We discuss the perspective of targeting this cascade for cancer treatment and weigh its chances and potential risks when considering its emerging role as a protective stress response pathway.},
  language  = {en}
}