Mechanical stress stimulates the osteo/odontoblastic differentiation of human stem cells from apical papilla via erk 1/2 and JNK MAPK pathways.
BACKGROUND
Stem cells from apical papilla (SCAPs) are a potent candidate for the apexogenesis/apexification due to their multiple differentiation capacity. During the orthodontic treatment of developing teeth, SCAPs in vivo are usually subjected to the cyclic stress induced by compression forces. However, it remains unclear whether mechanical stress can affect the proliferation and differentiation of human SCAPs.


RESULTS
Human SCAPs were isolated and stimulated by 200 g mechanical stimuli for 30 min and their proliferation and differentiation capacity were evaluated in vitro at different time points. MTT and FCM results demonstrated that cell proliferation was enhanced, while TEM findings showed the morphological and ultrastructural changes in stress-treated SCAPs. ALP activity and mineralization capacity of stress-treated SCAPs were upregulated . In the meantime, higher odontogenic and osteogenic differentiation were found in stress-treated SCAPs by real-time RT-PCR and Western blot, as indicated by the expression of related markers at both mRNA and protein levels. Moreover, the protein expressions of pJNK and pERK MAPK pathways were upregulated.


CONCLUSIONS
Together, these findings suggest that mechanical stress is an important factor affecting the proliferation and differentiation of SCAPs via the activation of ERK and JNK signaling pathway.
State Key Laboratory of Reproductive Medicine, Department of Stomatology, Nanjing Maternity and Child Health Care Hospital Affiliated to Nanjing Medical University, Nanjing, Jiangsu 210029, China.
Chao
C
Mu
State Key Laboratory of Reproductive Medicine, Department of Stomatology, Nanjing Maternity and Child Health Care Hospital Affiliated to Nanjing Medical University, Nanjing, Jiangsu 210029, China.
Taohong
T
Lv
Institute of Stomatology, School of Stomatology, Nanjing Medical University, 136 Hanzhong Road, Nanjing, Jiangsu 210029, China.
Zilu
Z
Wang
Endodontic Department, School of Stomatology, Nanjing Medical University, 136 Hanzhong Road, Nanjing, Jiangsu 210029, China.
Shu
S
Ma
State Key Laboratory of Reproductive Medicine, Department of Stomatology, Nanjing Maternity and Child Health Care Hospital Affiliated to Nanjing Medical University, Nanjing, Jiangsu 210029, China.
Jie
J
Ma
State Key Laboratory of Reproductive Medicine, Department of Stomatology, Nanjing Maternity and Child Health Care Hospital Affiliated to Nanjing Medical University, Nanjing, Jiangsu 210029, China.
Jin
J
Liu
Institute of Stomatology, School of Stomatology, Nanjing Medical University, 136 Hanzhong Road, Nanjing, Jiangsu 210029, China ; Endodontic Department, School of Stomatology, Nanjing Medical University, 136 Hanzhong Road, Nanjing, Jiangsu 210029, China.
Jinhua
0000-0003-4874-9910
J
Yu
State Key Laboratory of Reproductive Medicine, Department of Stomatology, Nanjing Maternity and Child Health Care Hospital Affiliated to Nanjing Medical University, Nanjing, Jiangsu 210029, China.
Jinquan
J
Mu
D000293:Adolescent; D000469:Alkaline Phosphatase / Q000378:metabolism; D015153:Blotting, Western; D002454:Cell Differentiation; D049109:Cell Proliferation; D048430:Cell Shape; D003771:Dental Papilla / Q000166:cytology*; D057075:Enzyme Assays; D006801:Humans; D007150:Immunohistochemistry; D020935:MAP Kinase Signaling System; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D009804:Odontoblasts / Q000166:cytology / Q000201:enzymology; D010006:Osteoblasts / Q000166:cytology / Q000201:enzymology; D060888:Real-Time Polymerase Chain Reaction; D013234:Stem Cells / Q000166:cytology* / Q000201:enzymology / Q000648:ultrastructure; D013314:Stress, Mechanical; D055815:Young Adult
D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D000469:Alkaline Phosphatase