G protein-coupled calcium-sensing receptor is a crucial mediator of MTA-induced biological activities

Mineral trioxide aggregate suppresses pro‐inflammatory cytokine expression via the calcineurin/nuclear factor of activated T cells/early growth response 2 pathway in lipopolysaccharide‐stimulated macrophages

“…The biological properties of MTA have been attributed to the bioactivity of this material, which involves continuous release of Ca 2+ (Cavenago et al 2014) and subsequent nucleation of apatite deposits on the material surface (Yamamoto et al 2017). Moreover, MTA induces intracellular mobilization of Ca 2+ through activation of the extracellular calcium-sensing receptor (CaSR) in human dental pulp cells (Kim et al 2017). The resultant enhancement of intracellular Ca 2+ may activate downstream signalling pathways such as Wnt (Yaemkleebbua et al 2019), calcineurin/nuclear factor of activated T cells (NFAT) and mitogen-activated protein kinase (Clapham 2007).…”

The emerging role of extracellular Ca2+ in osteo/odontogenic differentiation and the involvement of intracellular Ca2+ signaling: From osteoblastic cells to dental pulp cells and odontoblasts

“…Interestingly, ERK and JNK phosphorylation can be inhibited by nifedipine, an L-type Ca 2+ channel blocker (Woo et al, 2013), but no inhibitory effect of nifedipine was observed in p38 phosphorylation, suggesting that Ca 2+ influx through L-type Ca 2+ channels is required for the selective activation of ERK and seems to operate independently of p38 signaling (Mulvaney, Zhang, Fewtrell, & Roberson, 1999;Tada et al, 2010). In addition to L-type Ca 2+ channels, CaSRs have also been confirmed to mediate MTA-induced biological reactions in several recent studies (J. M. Kim et al, 2017;Mizumachi et al, 2017;Yasukawa et al, 2017). Additionally, a mixture of MTA with 5% CaCl 2 and 2.5% Na 2 HPO 4 promoted better differentiation in human DPCs than conventional MTA alone via the upregulation of DSPP and COL1 gene expression (Kulan, Karabiyik, Kose, & Kargul, 2017), supporting the concept that extracellular Ca 2+ and P ions could combinatorially affect osteo/odontoblastic differentiation induced by MTA through the targeting of osteoblast marker expression.…”

“…Li, Cao, Fan, & Xu, 2015). These improvements may be, in part, due to osteo/odontogenic differentiation of human DPCs induced by the higher levels of Ca 2+ released from MTA (Dudeja, Kumari, Singh, & Taneja, 2015) and mobilization of Ca 2+ , silicon, and strontium ions via the activation of Ca 2+ channels (e.g., CaSR) and MAPK pathways (J. M. Kim et al, 2017;Mizumachi et al, 2017;Wu et al, 2014). Furthermore, H. Zhang, Shen, Ruse, and Haapasalo (2009) over a 28-day period at pH 7.0, while at pH 5.5 these levels dropped significantly, by 24%, after 21 days (Natale et al, 2015).…”

Enhanced calcium ion mobilization in osteoblasts on amino group containing plasma polymer nanolayer

“…A short-term rise of Ca 2+ is important for signal transmission, and intracellular calcium dynamic is triggered by a variety of factors like adenosine triphosphate (ATP) [ 14 , 17 , 18 ] or mechanical forces [ 10 , 13 ]. The ligand ATP typically activates the cell-surface G protein-coupled receptor (GPCR) which generates inositol-1,4,5-triphosphate (IP3); this induces transient and rapid Ca 2+ -release through activation of its receptor which is located in the membrane of the internal Ca 2+ -store, the smooth endoplasmic reticulum (ER) [ 14 , 15 , 19 ]. Intracellular Ca 2+ as a second messenger system is responsible for signal transduction [ 14 ] e.g.…”

“…So, external signals provide a distinct Ca 2+ dynamic that selectively controls long-term cellular responses like proliferation [ 20 ] and differentiation [ 10 , 14 , 15 ] by, e.g. binding and activation of other downstream signal proteins and transcription factors [ 13 , 17 , 19 ]. To study the role of the intracellular Ca 2+ dynamic on different chemical surface compositions, osteoblasts were stained with a very common non-ratiometric (single wavelength) Ca 2+ indicator fluo-3 [ 16 , 21 ] and analyzed using confocal laser scanning microscopy.…”