Cementum protein 1 (CEMP1) activates p38 and JNK during the mineralisation process by cementoblast-like cells in vitro

We recently presented evidence showing that cementum protein 1 (CEMP1) promotes periodontal ligament (PDL) cell migration, proliferation, expression of bone, and cementum-matrix proteins and mineralisation. In other words, it induces PDL precursor cells commitment toward a cementoblast-like cells phenotype. The intracellular signalling pathways involved in cementoblast differentiation and mineralisation have not been well characterised. JNK and p38 protein kinases (MAPKs) are intracellular signalling pathways and key mediators of cellular processes such as proliferation and differentiation. Since signalling pathways involving MAPKs have been associated with osteoblastic phenotype, in this study we investigated the effect of hrCEMP1 and mineralising media containing β-glycerophosphate and ascorbic acid on the activation of p38-MAPK and JNK–MAPK in cementoblast-like cells. Our results show that mineralising media and hrCEMP1 induced phosphorylation of p38 and JNK kinases. Mineralising media containing hrCEMP1 increased the activation of p38-MAPK and its translocation to the cell nucleus; increased phosphorylation of JNK–MAPK and induced the phosphorylation of the protein C-JUN. We also demonstrate that hrCEMP1 regulates the expression of BSP, OCN, and ALP specific activity. We found that hrCEMP1 and mineralising media promote nodule formation. These findings give an insight into the signalling pathways activated by hrCEMP1 and suggest likely components of the mechanisms that regulate the formation and regeneration of cementum and surrounding connective tissues.