Slug contributes to the regulation of CXCL12 expression in human osteoblasts

Roberta Piva, Cristina Manferdini, Elisabetta Lambertini, Elena Torreggiani, Letizia Penolazzi, Roberto Gambari, Antonio Pastore, Stefano Pelucchi, Elena Gabusi, Anna Piacentini, Giuseppe Filardo, Andrea Facchini, Gina Lisignoli

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)1159-1168
Number of pages10
JournalExperimental Cell Research
Volume317
Issue number8
DOIs
Publication statusPublished - May 1 2011

    Fingerprint

Keywords

  • Chromatin immunoprecipitation
  • CXCL12 chemokine
  • Gene regulation
  • Human osteoblasts
  • Slug
  • Small interfering RNA

ASJC Scopus subject areas

  • Cell Biology

Cite this

Piva, R., Manferdini, C., Lambertini, E., Torreggiani, E., Penolazzi, L., Gambari, R., Pastore, A., Pelucchi, S., Gabusi, E., Piacentini, A., Filardo, G., Facchini, A., & Lisignoli, G. (2011). Slug contributes to the regulation of CXCL12 expression in human osteoblasts. Experimental Cell Research, 317(8), 1159-1168. https://doi.org/10.1016/j.yexcr.2010.12.011