
Research Unit "Regeneration in aged"
The Research Unit 2165 Regeneration in Aged Individuals: Using Bone Healing as a Model System to Characterise Regeneration under Compromised Conditions aims to understand the basic mechanisms that impede the otherwise effective healing process along the two pathways of early immune response and restoration of mechanical competence through aging.
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Project 3 - Principal Investgators
CRC 1444 Representative of partner university & Education of early career scientists, Subprojects 3 & 4 | RU 2165 Subprojects 3


Mechanical strain and BMP-stimulation instruct the extracellular matrix to control stem cell fate decisions: an age-dependent matrix code?

Already in the very early phase of bone fracture healing, a complex extracellular matrix (ECM) network is assembled. The biochemical and mechanical signals provided by the ECM are believed to instruct cell fate and function. We hypothesize that the information encoded in the ECM is modulated by the physico-chemical stimuli present during its formation and that the stored information will be sensed by cells much longer than the stimuli were present. We will build ECM in 3D microtissue culture under control of mechanical straining and bone morphogenetic proteins (BMPs) and perform careful mechanical and biochemical characterization. We will furthermore study the instructiveness of decellularized matrices on bone progenitor cells and investigate the influence of ageing on the encoding and reading process. We propose that the ECM plays a relevant role as an age-dependent memory for mechanical and biochemical signals during bone regeneration.
Publications
- Authors:Schreivogel, S.; Kuchibhotla, V.; Knaus, P.; Duda, G. N., Petersen, A.
Journal:J Tissue Eng Regen Med Year:2019; Volume:13Issue:(11):Pages:1992-2008.
Title:Load-induced osteogenic differentiation of mesenchymal stromal cells is caused by mechano-regulated autocrine signaling - Authors:Brauer, E.; Lippens, E.; Klein, O.; Nebrich, G.; Schreivogel, S.; Korus, G.; Duda, G. N.; Petersen, A.
Journal:Adv Sci (Weinh) Year:2019; Volume:9Issue:(6):Pages:1801780.
Title:Collagen Fibrils Mechanically Contribute to Tissue Contraction in an In Vitro Wound Healing Scenario - Authors:Schwarz, C.; Ott, C. E.; Wulsten, D.; Brauer, E; Schreivogel, S.; Petersen, A.; Hassanein, K.; Roewer, L.; Schmidt, T.; Willie, B. M.; Duda, G. N.
Journal:JBMR Plus Year:2018; Volume:2Issue:(3):Pages:174-186.
Title:The Interaction of BMP2-Induced Defect Healing in Rat and Fixator Stiffness Modulates Matrix Alignment and Contraction - Authors:Heinks, T.; Hettwer, A.; Hiepen, C.; Weise, C.; Gorka, M.; Knaus, P.; Mueller, T. D.; Loidl-Stahlhofen, A.
Journal:Protein Expr Purif Year:2021; Volume:186:Pages:105918.
Title:Optimized expression and purification of a soluble BMP2 variant based on in-silico design - Authors:Hiepen, C.; Jatzlau, J.; Hildebrandt, S.; Kampfrath, B.; Goktas, M.; Murgai, A.; Cuellar Camacho, J. L.; Haag, R.; Ruppert, C.; Sengle, G.; Cavalcanti-Adam, E. A.; Blank, K. G.; Knaus, P.
Journal:PLoS Biol Year:2019; Volume:17Issue:(12):Pages:e3000557.
Title:BMPR2 acts as a gatekeeper to protect endothelial cells from increased TGFbeta responses and altered cell mechanics - Authors:Hiepen, C.; Jatzlau, J.; Knaus, P.
Journal:Cell Stress Year:2020; Volume:4Issue:(2)
Title:Biomechanical stress provides a second hit in the establishment of BMP/TGFbeta-related vascular disorders - Authors:Hiepen, C.; Mendez, P. L.; Knaus, P.
Journal:Cells Year:2020; Volume:9Issue:(9)
Title:It Takes Two to Tango: Endothelial TGFbeta/BMP Signaling Crosstalk with Mechanobiology - Authors:Hildebrandt, S.; Kampfrath, B.; Fischer, K.; Hildebrand, L.; Haupt, J.; Stachelscheid, H.; Knaus, P.
Journal:Stem Cell Rev Rep Year:2021; Volume:17Issue:(3):Pages:1039-1052.
Title:ActivinA Induced SMAD1/5 Signaling in an iPSC Derived EC Model of Fibrodysplasia Ossificans Progressiva (FOP) Can Be Rescued by the Drug Candidate Saracatinib - Authors:da Silva Madaleno, C.; Jatzlau, J.; Knaus, P.
Journal:Bone Year:2020; Volume:137:Pages:115416.
Title:BMP signalling in a mechanical context - Implications for bone biology - Authors:Reichenbach, M.;Mendez, P. L.; da Silva Madaleno, C.; Ugorets, V.; Rikeit, P.; Boerno, S.; Jatzlau, J.; Knaus, P.
Journal:Adv Biol (Weinh) Year:2021; Volume:5Issue:(2):Pages:e2000051.
Title:Differential Impact of Fluid Shear Stress and YAP/TAZ on BMP/TGF-beta Induced Osteogenic Target Genes