Effects of fibroblast growth factor-2 on the expression and regulation of chemokines in human dental pulp cells.
BACKGROUND
Fibroblast growth factor-2 (FGF-2) participates in both hematopoiesis and osteogenesis; however, the effects of FGF-2 on chemokines during odontoblastic differentiation have not been reported. This study investigated whether human dental pulp cells (HDPCs) treated with FGF-2 could express chemokines during differentiation into odontoblastic cells and sought to identify its underlying mechanism of action.


METHODS
To analyze differentiation, we measured alkaline phosphatase (ALP) activity, calcified nodule formation by alizarin red staining, and marker RNA (mRNA) expression by reverse-transcriptase polymerase chain reaction (RT-PCR). Expression of chemokines, such as interleukin-6 (IL-6), IL-8, monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein-1α (MIP-1α), and MIP-3α, were evaluated by RT-PCR.


RESULTS
ALP activity, the mineralization, and mRNA expression for odontoblastic markers were enhanced by FGF-2 in HDPCs. FGF-2 also up-regulated the expression of IL-6, IL-8, MCP-1, MIP-1α, and MIP-3α mRNAs, which were attenuated by inhibitors of p38, ERK1/2 and p38 MAP kinases, protein kinase C, phosphoinositide-3 kinase, and NF-κB.


CONCLUSIONS
Taken together, these data suggest that FGF-2 plays a role not only as a differentiation inducing factor in the injury repair processes of pulpal tissue but also as a positive regulator of chemokine expression, which may help in tissue engineering and pulp regeneration using HDPCs. However, the fate of odontoblastic or osteoblastic differentiation, effective local delivery for FGF-2, interaction of chemotatic and odontogenic factors, and other limitations will need to be overcome before a major modality for the treatment of pulp disease.
Department of Oral and Maxillofacial Pathology, School of Dentistry and Institute of Wonkwang Dental Research, Wonkwang University, Iksan, South Korea.
Young-Suk
YS
Kim
Kyung-San
KS
Min
Dong-Ho
DH
Jeong
Jun-Hyeog
JH
Jang
Hae-Won
HW
Kim
Eun-Cheol
EC
Kim
D000469:Alkaline Phosphatase / Q000032:analysis; D000880:Anthraquinones; D002113:Calcification, Physiologic / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D018932:Chemokine CCL2 / Q000032:analysis; D054418:Chemokine CCL20 / Q000032:analysis; D054405:Chemokine CCL3 / Q000032:analysis; D018925:Chemokines / Q000187:drug effects*; D004396:Coloring Agents; D003782:Dental Pulp / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D005819:Genetic Markers / Q000235:genetics; D006801:Humans; D015850:Interleukin-6 / Q000032:analysis; D016209:Interleukin-8 / Q000032:analysis; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D009804:Odontoblasts / Q000187:drug effects; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D012313:RNA / Q000032:analysis; D015398:Signal Transduction / Q000187:drug effects; D013234:Stem Cells / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors
D000880:Anthraquinones; C111835:CCL2 protein, human; D018932:Chemokine CCL2; D054418:Chemokine CCL20; D054405:Chemokine CCL3; D018925:Chemokines; D004396:Coloring Agents; D004791:Enzyme Inhibitors; D005819:Genetic Markers; D015850:Interleukin-6; D016209:Interleukin-8; D016328:NF-kappa B; D000081082:Phosphoinositide-3 Kinase Inhibitors; D016222:Fibroblast Growth Factor 2; C010078:alizarin; D012313:RNA; D011493:Protein Kinase C; D048051:p38 Mitogen-Activated Protein Kinases; D000469:Alkaline Phosphatase