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Related Concept Videos

Cell-matrix's Response to Mechanical Forces01:13

Cell-matrix's Response to Mechanical Forces

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In animal cells, the extracellular matrix allows cells within tissues to withstand external stresses and transmits signals from the outside of the cell to the inside. The extracellular matrix is extensive, and its composition varies between different types of tissues. For example, the reticular fibers and ground substance make up the ECM in loose connective tissue, while collagen and bone minerals make up the ECM of bone tissue. 
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Unlike epithelial tissue, which is composed of cells closely packed with little or no extracellular space in between, connective tissue cells are dispersed in a matrix. This extracellular matrix (ECM) is composed of fibrous proteins like collagen, elastin, and fibronectin in a ground substance consisting of interstitial fluid, cell adhesion proteins, and proteoglycans. The proteoglycans form a gel-like material in the spaces between cells and provide hydration, buffering, binding, and force...
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In order to maintain tissue organization, many animal cells are surrounded by structural molecules that make up the extracellular matrix (ECM). Together, the molecules in the ECM maintain the structural integrity of tissue as well as the remarkable specific properties of certain tissues.
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Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
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Extracellular Matrix Stiffness Regulates Osteogenic Differentiation through MAPK Activation.

Jun-Ha Hwang1, Mi Ran Byun1, A Rum Kim1

  • 1Department of Life Sciences, School of Life Sciences and Biotechnology, Korea University, Seoul, Korea.

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Extracellular matrix stiffness regulates mesenchymal stem cell (MSC) differentiation. Stiff matrices activate ERK/JNK pathways, promoting osteogenic differentiation via TAZ nuclear localization and inhibiting adipogenic differentiation.

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Area of Science:

  • Biomedical Engineering
  • Cell Biology
  • Stem Cell Research

Background:

  • Mesenchymal stem cell (MSC) differentiation is influenced by the extracellular matrix (ECM).
  • ECM stiffness is a key regulator of MSC fate.
  • Transcriptional coactivator with PDZ-binding motif (TAZ) is an effector in MSC differentiation, but its precise role in response to ECM stiffness is unclear.

Purpose of the Study:

  • To elucidate the mechanism by which ECM stiffness regulates MSC differentiation via TAZ.
  • To investigate the role of ERK and JNK signaling pathways in ECM stiffness-mediated MSC fate determination.

Main Methods:

  • Utilized hydrogel matrices of varying stiffness to culture MSCs.
  • Assessed MSC differentiation towards osteogenic and adipogenic lineages.
  • Measured nuclear localization of TAZ.
  • Analyzed the activity of ERK and JNK signaling pathways, including the use of specific inhibitors.

Main Results:

  • Stiff ECM promoted osteogenic differentiation and inhibited adipogenic differentiation.
  • Increased nuclear localization of TAZ was observed on stiff matrices.
  • Stiff hydrogels significantly increased ERK and JNK pathway activity.
  • Inhibition of ERK or JNK pathways reduced TAZ nuclear localization, indicating their necessity for TAZ activation on stiff matrices.

Conclusions:

  • ECM stiffness regulates MSC differentiation through the activation of ERK and/or JNK signaling pathways.
  • ERK/JNK activation on stiff matrices is crucial for TAZ-mediated osteogenic differentiation.
  • These findings reveal a signaling cascade linking mechanical cues from the ECM to stem cell fate determination.