CEMP1 Induces Transformation in Human Gingival Fibroblasts.

Mercedes Bermúdez,Claudia Rangel-Escareño,Higinio Arzate,Ivan Imaz-Rosshandler,Margarita Zeichner-David,Gabriela E Mercado-Celis,Philip C Trackman

doi:10.1371/journal.pone.0127286

Abstract

Cementum Protein 1 (CEMP1) is a key regulator of cementogenesis. CEMP1 promotes cell attachment, differentiation, deposition rate, composition, and morphology of hydroxyapatite crystals formed by human cementoblastic cells. Its expression is restricted to cementoblasts and progenitor cell subpopulations present in the periodontal ligament. CEMP1 transfection into non-osteogenic cells such as adult human gingival fibroblasts results in differentiation of these cells into a “mineralizing” cell phenotype. Other studies have shown evidence that CEMP1 could have a therapeutic potential for the treatment of bone defects and regeneration of other mineralized tissues. To better understand CEMP1’s biological effects in vitro we investigated the consequences of its expression in human gingival fibroblasts (HGF) growing in non-mineralizing media by comparing gene expression profiles. We identified several mRNAs whose expression is modified by CEMP1 induction in HGF cells. Enrichment analysis showed that several of these newly expressed genes are involved in oncogenesis. Our results suggest that CEMP1 causes the transformation of HGF and NIH3T3 cells. CEMP1 is overexpressed in cancer cell lines. We also determined that the region spanning the CEMP1 locus is commonly amplified in a variety of cancers, and finally we found significant overexpression of CEMP1 in leukemia, cervix, breast, prostate and lung cancer. Our findings suggest that CEMP1 exerts modulation of a number of cellular genes, cellular development, cellular growth, cell death, and cell cycle, and molecules associated with cancer.

Highlights

Cementum extracellular matrix contains specific molecules expressed by cementoblasts and their progenitor cells present in the periodontal ligament
The data shows background expression of Cementum Protein 1 (CEMP1) in both cell lines at day 0, after 3 days in culture, CEMP1 expression was significantly higher in the human gingival fibroblasts (HGF)/CEMP1 while no changes were seen in the HGF cells alone, demonstrating that both, mRNA and protein are expressed in these cells
The findings indicated a good concordance of expression profiles between the microarray and quantitative real-time polymerase chain reaction (PCR) (qRT-PCR) results (Table 1)

Summary

Introduction

Cementum extracellular matrix contains specific molecules expressed by cementoblasts and their progenitor cells present in the periodontal ligament. Amongst these unique molecules, Cementum Attachment Protein (PTPLa/CAP) and Cementum Protein 1 (CEMP1) are believed to regulate the biological activities of periodontal ligament cells [1,2,3,4,5,6]. The presence of PLOS ONE | DOI:10.1371/journal.pone.0127286. CEMP1 Fibroblasts Transformation in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Methods

Results

Discussion

Conclusion