CEMP1 Induces Transformation in Human Gingival Fibroblasts

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.

rhBMP-2 Pre-Treated Human Periodontal Ligament Stem Cell Sheets Regenerate a Mineralized Layer Mimicking Dental Cementum

“…To further investigate the regeneration outcome of the transplanted hPDLSCs, expressions of cementogenic and osteogenic markers were evaluated. The expression of CEMP-1, which indicates the activity of cementoblasts and their progenitors [6,24] in group B, demonstrated that rhBMP-2-hPDLSC sheets promoted cementum-like mineralized structure formation ( Figure 5B). In terms of osteogenic differentiation, ALP expression for the early stage was not detectable in any groups, but OCN expression for the late stage differed between the control group and the hPDLSC sheet groups ( Figure 5B).…”

Cementum protein 1 transfection does not lead to ultrastructural changes in nucleolar organization of human gingival fibroblasts

“…These cells are considered as putative cementoblasts because they increase the rate of proliferation, synthetize mineralized extracellular matrix (biological‐type hydroxyapatite), and express higher alkaline phosphatase activity and biomineralization‐related and cementum‐specific proteins . Microarray studies show that CEMP1 can modulate the expression of several genes related to cellular development, cellular growth, cell cycle, and cell death in HGFs transfected with CEMP1 . Thus, the effect of CEMP1 in HGFs is known at the transcriptional level but not at the ultrastructural level.…”

Efeito da ativação do receptor ativado por protease do tipo 1 (PAR1) sobre as atividades osteogênica e cementogênica de células mesenquimais do ligamento periodontal

“…Para que ela ocorra, diversas moléculas presentes na matriz extra-celular devem atuar na proliferação e diferenciação cementoblástica, assim como na formação de uma nova matriz de cemento . CEMP1 é a principal proteína reguladora da cementogênese, ele desempenha papel importante no metabolismo local, regulando a diferenciação cementoblástica e a indução da deposição de cemento (Bermúdez et al, 2015).…”

“…A cementogênese é considerada o processo mais importante da regeneração periodontal (Cortellini;Tonetti, 2015). Em nosso estudo, a ativação do PAR1 aumentou a expressão gênica de CEMP1, proteína que atua regulando a diferenciação cementoblástica e formação de matrix de cemento (Bermúdez et al, 2015). Por outro lado, nossos resultados indicam que a ativação do PAR1 não tem efeito na expressão gênica de CAP.…”