title: Slug contributes to the regulation of CXCL12 expression in human osteoblasts.
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.
authors.affiliation: Dipartimento di Biochimica e Biologia Molecolare, Università degli Studi di Ferrara, Via Fossato di Mortara, Ferrara, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Piva
authors.forename: Cristina
authors.initials: C
authors.lastname: Manferdini
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Lambertini
authors.forename: Elena
authors.initials: E
authors.lastname: Torreggiani
authors.forename: Letizia
authors.initials: L
authors.lastname: Penolazzi
authors.forename: Roberto
authors.initials: R
authors.lastname: Gambari
authors.forename: Antonio
authors.initials: A
authors.lastname: Pastore
authors.forename: Stefano
authors.initials: S
authors.lastname: Pelucchi
authors.forename: Elena
authors.initials: E
authors.lastname: Gabusi
authors.forename: Anna
authors.initials: A
authors.lastname: Piacentini
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Filardo
authors.forename: Andrea
authors.initials: A
authors.lastname: Facchini
authors.forename: Gina
authors.initials: G
authors.lastname: Lisignoli
mesh_terms: D002478:Cells, Cultured; D054377:Chemokine CXCL12 / Q000235:genetics / Q000378:metabolism*; D047369:Chromatin Immunoprecipitation; D020868:Gene Silencing; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000502:physiology; D010006:Osteoblasts / Q000166:cytology / Q000502:physiology*; D011401:Promoter Regions, Genetic; D015398:Signal Transduction / Q000502:physiology; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D054377:Chemokine CXCL12; C000604407:SNAI1 protein, human; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors