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Cell and Extracellular Matrix Interactions in a Dynamic Biomechanical Environment:
Published in Michel R. Labrosse, Cardiovascular Mechanics, 2018
Like other GTPases, Rho is inactive when bound to guanosine diphosphate (GDP) and is activated by guanine-nucleotide exchange factors (GEFs), which catalyze the exchange of GDP for GTP (Lessey et al. 2012). Rho’s intrinsic GTPase activity can revert its active GTP-bound form to the inactive GDP-bound form, but this process can be catalyzed by GTPase-activating proteins (GAPs). Rho can be activated by a variety of mechanical forces, including shear stress, compression, and tension (Lessey et al. 2012). This process is mediated by GEFs and GAPs that associate with the cytoskeleton and focal adhesions (Schwartz 2004, Lessey et al. 2012). Notably, FAK can activate Rho directly by binding and phosphorylating p190RhoGEF (Lim et al. 2008) and can inactivate Rho indirectly through Src to phosphorylate p190RhoGAP (Schober et al. 2007). RhoA’s control of the actin–myosin machinery makes it an important signaling protein, mediating changes to cell structural behaviors such as cell shape response and migration in response to mechanical stimuli (Arthur and Burridge 2001, Peyton and Putnam 2005, Liu et al. 2014). While RhoA activity can change cell shape, cell shape itself can modulate RhoA levels and cytoskeletal tension and provide important developmental cues, with spread, flattened MSCs undergoing osteogenesis and unspread, rounded MSCs undergoing adipogenesis (McBeath et al. 2004). The ECM through structural organization, mechanical properties, and transmission of mechanical forces is an important regulator of cell shape, but cells can maintain a degree of control by actively remodeling the ECM with MMPs to assume cell shapes favorable to different differentiation fates (Figure 2.9) (Tang et al. 2013). Extracellular matrix stiffness also acts through RhoA signaling to direct MSC differentiation (Engler et al. 2006). RhoA activity controls the shuttling of transcriptional coactivators such as four and a half LIM domains protein 2 (FHL2) (Muller et al. 2002) and yes-associated protein (YAP)/tafazzin (TAZ) (Tang et al. 2013, Panciera et al. 2017) between the cytoplasm and the nucleus to regulate gene transcription.
Synthetic electrospun nanofibers as a supportive matrix in osteogenic differentiation of induced pluripotent stem cells
Published in Journal of Biomaterials Science, Polymer Edition, 2022
Arash Azari Matin, Khashayar Fattah, Sahand Saeidpour Masouleh, Reza Tavakoli, Seyed Armin Houshmandkia, Afshin Moliani, Reza Moghimimonfared, Sahar Pakzad, Elaheh Dalir Abdolahinia
Dexamethasone (DEX), ascorbic acid, and β‐glycerophosphate (βGP) are the common osteoinductive inducers. DEX is a synthetic glucocorticoid with anti-inflammatory effects. It is widely used for the osteogenic differentiation of stem cells from various sources. Osteogenic differentiation is characterized by three stages including proliferation, ECM maturation, and mineralization. It is shown that DEX involves in the early stage of osteogenic differentiation as well as osteoblast maturation and mineralization [140]. Studies have shown that DEX increases the expression of OC and bone sialoprotein (BSP) [141]. DEX induces the expression and activation of Runx2 by activating FHL2, β-catenin-like molecule TAZ, and mitogen-activated protein kinase (MAPK) phosphatase-1 (MKP-1) transcription factors (Figure 3) [142]. DEX increased the activity of ALP [143] however; it decreased the expression of collagen I [144]. Therefore, it is essential to use other inducers along with DEX for osteogenic differentiation. Ascorbic acid which is known as vitamin C is another osteogenic inducer. Unlike DEX, ascorbic acid is involved in the formation of collagen I from procollagen and its secretion into ECM. Subsequently, collagen I acts on integrin and activates MAPK/extracellular related kinase (ERK) pathway which enhances the Runx2 activity [142]. βGP is mainly involved in dystrophic mineralization. It serves as a phosphate source for bone minerals. It also induces the phosphorylation of ERK which activate the ERK signaling pathway, resulting in the induction of osteogenic genes including bone morphogenetic proteins (BMP) 2 and OC [142].