Products of dentin matrix protein-1 degradation by interleukin-1β-induced matrix metalloproteinase-3 promote proliferation of odontoblastic cells.
We have previously reported that interleukin (IL)-1β induces matrix metalloproteinase (MMP)-3-regulated cell proliferation in mouse embryonic stem cell (ESC)-derived odontoblast-like cells, suggesting that MMP-3 plays a potentially unique physiological role in regeneration by odontoblast-like cells. MMPs are able to process virtually any component of the extracellular matrix, including collagen, laminin and bioactive molecules. Because odontoblasts produce dentin matrix protein-1 (DMP-1), we examined whether the degraded products of DMP-1 by MMP-3 contribute to enhanced proliferation in odontoblast-like cells. IL-1β increased mRNA and protein levels of odontoblastic marker proteins, including DMP-1, but not osteoblastic marker proteins, such as osteocalcin and osteopontin. The recombinant active form of MMP-3 could degrade DMP-1 protein but not osteocalcin and osteopontin in vitro. The exogenous degraded products of DMP-1 by MMP-3 resulted in increased proliferation of odontoblast-like cells in a dose-dependent manner. Treatment with a polyclonal antibody against DMP-1 suppressed IL-1β-induced cell proliferation to a basal level, but identical treatment had no effect on the IL-1β-induced increase in MMP-3 expression and activity. Treatment with siRNA against MMP-3 potently suppressed the IL-1β-induced increase in DMP-1 expression and suppressed cell proliferation (p < 0.05). Similarly, treatment with siRNAs against Wnt5a and Wnt5b suppressed the IL-1β-induced increase in DMP-1 expression and suppressed cell proliferation (p < 0.05). Rat KN-3 cells, representative of authentic odontoblasts, showed similar responses to the odontoblast-like cells. Taken together, our current study demonstrates the sequential involvement of Wnt5, MMP-3, DMP-1 expression, and DMP-1 degradation products by MMP-3, in effecting IL-1β-induced proliferation of ESC-derived odontoblast-like cells.
Department of Endodontics, School of Dentistry, Aichi Gakuin University.
Naoko
N
Hase
Nobuaki
N
Ozeki
Taiki
T
Hiyama
Hideyuki
H
Yamaguchi
Rie
R
Kawai
Ayami
A
Kondo
Kazuhiko
K
Nakata
Makio
M
Mogi
D000818:Animals; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism*; D053583:Interleukin-1beta / Q000494:pharmacology*; D019278:Matrix Metalloproteinase 3 / Q000378:metabolism*; D051379:Mice; D008954:Models, Biological; D009804:Odontoblasts / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology*; D015675:Osteocalcin / Q000378:metabolism; D053495:Osteopontin / Q000235:genetics / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism*; D059748:Proteolysis / Q000187:drug effects*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats
C513308:Dmp1 protein, mouse; C081635:Dmp1 protein, rat; D016326:Extracellular Matrix Proteins; D053583:Interleukin-1beta; D010750:Phosphoproteins; D012333:RNA, Messenger; D015675:Osteocalcin; D053495:Osteopontin; D019278:Matrix Metalloproteinase 3