Ballini, Andrea

Brunetti, Giacomina

Carbone, Claudia

Colucci, Silvia

Grano, Maria

Grassi, Roberto

Mori, Giorgio

Oranger, Angela

Sardone, Francesca

Firenze University Press: E-Journals

IJAE Vol. 115, n. 1/2 (Supplement), 2010
119
Dental Pulp Stem Cells (DPSCs), differentiating into 
osteoblasts, become a source of the pro-apoptotic 
factor TRAIL: evaluation of an experimental model for 
cancer therapy
Giorgio Mori1, Giacomina Brunetti2, Angela Oranger2, Francesca Sardone2, Claudia Carbone2, An-
drea Ballini3, Roberto Grassi3, Silvia Colucci2, Maria Grano2
1 Dipartimento di Scienze Biomediche, Università di Foggia, Italy
2 Dipartimento di Anatomia Umana e Istologia “Rodolfo Amprino”, Università di Bari Italy
3 Dipartimento di Odontostomatologia e Chirurgia, Università di Bari Italy
The DPSCs belong to the family of mesenchymal stem cells (MSCs) and are capable, 
if properly stimulated to differentiate into different cell types including osteoblasts. It 
has been shown, in animal models, that MSCs derived from bone marrow, producing 
TNF-related apoptosis-inducing ligand (TRAIL), inhibit the growth of tumors that met-
astatize to the bone tissue, including lung cancer; however, the expression of TRAIL by 
the MSCs to be effective, must be stimulated with genetic engineering techniques with 
the involvement of bacterial vectors. TRAIL is a pro-apoptotic factor, member of the 
super-family of tumor necrosis factors, known for its peculiarity to selectively induce 
apoptosis in cancer cells. TRAIL can activate apoptotic signals by binding two different 
death receptors, DR4 and DR5. In our work we evaluated the production of TRAIL by 
DPSCs differentiated toward the osteoblastic phenotype. Microarray experiments, also 
supported by real-time PCR, showed that in DPSCs after differentiation, the expression 
of TRAIL increased fifteen times. Moreover, cell viability tests have shown that DPSCs 
differentiating into osteoblasts become resistant to the pro-apoptotic effect of the mol-
ecule. This strong resistance derives from a significant decrease in the expression of 
TRAIL receptors DR4 and DR5, and is confirmed by the weak activation of intracellular 
apoptotic signal (caspase 3) following the exposure to the molecule. Conversely, the 
tumor cell lines expressed high levels of DR4 and DR5, and in the presence of TRAIL, 
activate the intracellular apoptotic signals (caspase 3-8). Thus, the DPSCs, differenti-
ated into osteoblasts, expressing high levels of TRAIL and developing a resistance to 
the apoptotic effect of the molecule, could represent a valuable therapeutic approach to 
cancer therapy.
Keywords
DPSCs, stem cells, TRAIL, osteoblast differentiation, cancer cells apoptosis


Dental Pulp Stem Cells (DPSCs), differentiating into osteoblasts, become a source of the pro-apoptotic factor TRAIL: evaluation of an experimental model for cancer therapy

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Dental Pulp Stem Cells (DPSCs), differentiating into osteoblasts, become a source of the pro-apoptotic factor TRAIL: evaluation of an experimental model for cancer therapy

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