Sprouty 2 , an Early Response Gene Regulator of FosB and Mesenchymal Stem Cell Proliferation During Mechanical Loading and Osteogenic Differentiation

Abstract

Sprouty 2 (Spry2), an inhibitor of MAP kinase signaling was previously shown by our group to be induced during mechanical loading of mesenchymal stem cells (MSCs). Here, we studied the implication of Spry2 activation during mechanical loading and chemically induced MSC differentiation. Spry 2 expression showed an immediate early response during mechanical loading and chemical induction of osteogenic differentiation and followed the same pattern as osteogenic associated gene FosB and was necessary for the induction of FosB, as Spry 2 knock down also abrogated the upregulation of FosB expression. Spry 2 knock down was, also associated with an early response of the osteogenic genes Runx-2 and ALP. Neither the knock-down of Spry 2 nor the subsequent reduction in FosB had any effect on mid-late osteogenesis or mineralization but was associated with a significant increase in proliferation of MSC. These effects were possibly governed by negative regulation of MEK/Erk signaling as Spry 2 knock down resulted in an increase in phosphorylation of Erk1/2. In summary, our results shows the involvement of Spry2 in regulation of FosB and Runx2 genes, MAPK signaling and proliferation of MSC. Taken together these results suggest a possible role for Spry2 in regulation of MSC functions in response to mechanical loading and osteogenic differentiation. J. Cell. Biochem. 118: 2606-2614, 2017. © 2017 Wiley Periodicals, Inc.

Specification of Sprouty2 functions in osteogenesis in in vivo context

“…Modulation of Runx2 expression by SPRY2 was documented also in other system. 14 Regarding osteocytes identified by their typical marker, sclerostin, 16 Sost mRNA was strongly up-regulated in Spry2-/-tibias. Immunolabelling showed only a slight nonsignificant increase of SOST-positive osteocytes in Spry2-/-tibias.…”

“…Since Spry2 expression precedes the functional differentiation of osteoblasts, an effect on early osteogenesis was suspected. 13,14 Therefore, we searched for early consequences of SPRY2 deficiency in main bone cell types, osteoblasts, osteocytes and osteoclasts, during the prenatal formation of the growth plate in Spry2-/mice in vivo.…”

Newcastle Disease Virus V Protein Promotes Viral Replication in HeLa Cells through the Activation of MEK/ERK Signaling

“…The upstream regulators of the MEK/ERK pathway include SPRY2, which is an inhibitor of mitogen-activated protein kinase (MAPK) signaling. The knockdown of SPRY2 increases the phosphorylation of ERK1/2 [ 28 ]. We determined the mRNA levels of these molecules after treatment with ERK1/2 inhibitors, infection with NDV and overexpression of the V protein ( Figure 3 E).…”

Weighted gene correlation network analysis reveals novel biomarkers associated with mesenchymal stromal cell differentiation in early phase

“…In order to screen for candidate genes that can serve as potential biomarkers or therapeutic targets, the Phase I samples, associated with the brown module, were compared with the control samples, which led to the identification of 119 DEGs related to OS differentiation and 148 DEGs that were associated with AD differentiation. The identified DEGs were then compared with the brown module, which led to the identification of 13 common genes, including BHLHE40, FOSB (Schneider et al, 2017), CSRNP1, HBEGF (Li et al, 2019a), CLCF1 (Nahle et al, 2019), SPRY2 (Schneider et al, 2017), IL6 (Munir et al, 2017), PTGS2 (Feigenson et al, 2017), SGK1, FOXQ1, LIF (Huat et al, 2014), SERPINE1 (Karbiener et al, 2011) and ZNF281. Of interest, the previously identified OS differentiation-related genes FOSB, SPRY2 and PTGS2 were upregulated, while HBEGF, CLCF1 and LIF were downregulated.…”