TY - JOUR
T1 - Slug contributes to the regulation of CXCL12 expression in human osteoblasts
AU - Piva, Roberta
AU - Manferdini, Cristina
AU - Lambertini, Elisabetta
AU - Torreggiani, Elena
AU - Penolazzi, Letizia
AU - Gambari, Roberto
AU - Pastore, Antonio
AU - Pelucchi, Stefano
AU - Gabusi, Elena
AU - Piacentini, Anna
AU - Filardo, Giuseppe
AU - Facchini, Andrea
AU - Lisignoli, Gina
PY - 2011/5/1
Y1 - 2011/5/1
N2 - CXCL12/CXCR4 chemokine/receptor axis signaling has recently been found to play an important role in the remodeling of bone tissue, but little is known about the molecular mechanisms that are involved. The present study shows that CXCL12 is present at high levels both in human mesenchymal stem cells (hMSCs) and primary osteoblasts (hOBs). When osteogenesis was induced, CXCL12 expression was strictly confined to mineralized nodules. To investigate what mechanisms contribute to the maintenance of a correct expression of CXCL12 in bone cellular context, we analyzed the relationship between CXCL12 and Slug, a transcription factor recently associated with osteoblast maturation. By gene silencing and chromatin immunoprecipitation assay, we showed that both proteins are required for the mineralization process and CXCL12 is transcriptionally and functionally regulated by Slug, which is recruited at specific sites to its gene promoter in vivo.These findings showed for the first time a positive correlation between CXCL12 signaling and Slug activity, thus corroborating the role of these two proteins in bone cellular context and suggesting a new potential target for bone tissue repair and regeneration.
AB - CXCL12/CXCR4 chemokine/receptor axis signaling has recently been found to play an important role in the remodeling of bone tissue, but little is known about the molecular mechanisms that are involved. The present study shows that CXCL12 is present at high levels both in human mesenchymal stem cells (hMSCs) and primary osteoblasts (hOBs). When osteogenesis was induced, CXCL12 expression was strictly confined to mineralized nodules. To investigate what mechanisms contribute to the maintenance of a correct expression of CXCL12 in bone cellular context, we analyzed the relationship between CXCL12 and Slug, a transcription factor recently associated with osteoblast maturation. By gene silencing and chromatin immunoprecipitation assay, we showed that both proteins are required for the mineralization process and CXCL12 is transcriptionally and functionally regulated by Slug, which is recruited at specific sites to its gene promoter in vivo.These findings showed for the first time a positive correlation between CXCL12 signaling and Slug activity, thus corroborating the role of these two proteins in bone cellular context and suggesting a new potential target for bone tissue repair and regeneration.
KW - Chromatin immunoprecipitation
KW - CXCL12 chemokine
KW - Gene regulation
KW - Human osteoblasts
KW - Slug
KW - Small interfering RNA
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UR - http://www.scopus.com/inward/citedby.url?scp=79953119114&partnerID=8YFLogxK
U2 - 10.1016/j.yexcr.2010.12.011
DO - 10.1016/j.yexcr.2010.12.011
M3 - Article
C2 - 21182836
AN - SCOPUS:79953119114
VL - 317
SP - 1159
EP - 1168
JO - Experimental Cell Research
JF - Experimental Cell Research
SN - 0014-4827
IS - 8
ER -