Unique proliferation response in odontoblastic cells derived from human skeletal muscle stem cells by cytokine-induced matrix metalloproteinase-3

作者：Ozeki Nobuaki; Hase Naoko; Kawai Rie; Yamaguchi Hideyuki; Hiyama Taiki; Kondo Ayami; Nakata Kazuhiko; Mogi Makio^*

来源：Experimental Cell Research, 2015, 331(1): 105-114.

DOI：10.1016/j.yexcr.2014.09.015

• MMP-3
• Cytokine
• Inflammation
• Human stem cells
• Odontoblast

A pro-inflammatory cytokine mixture (CM: interleukin (IL-1 beta), tumor necrosis factor-alpha and interferon-gamma) and IL-1 beta-induced matrix metalloproteinase (MMP)-3 activity have been shown to increase the proliferation of rat dental pulp cells and murine stem cell-derived odontoblast-like cells. This suggests that MMP-3 may regulate wound healing and regeneration in the odontoblast-rich dental pulp. Here, we determined whether these results can be extrapolated to human dental pulp by investigating the effects of CM-induced MMP-3 up-regulation on the proliferation and apoptosis of purified odontoblast-like cells derived from human skeletal muscle stem cells. We used siRNA to specifically reduce MMP-3 expression. We found that CM treatment increased MMP-3 mRNA and protein levels as well as MMP-3 activity. Cell proliferation was also markedly increased, with no changes in apoptosis, upon treatment with CM and following the application of exogenous MMP-3. Endogenous tissue inhibitors of metalloproteinases were constitutively expressed during all experiments and unaffected by MMP-3. Although treatment with MMP-3 siRNA suppressed cell proliferation, it also unexpectedly increased apoptosis. This siRNA-mediated increase in apoptosis could be reversed by exogenous MMP-3. These results demonstrate that cytokine-induced MMP-3 activity regulates cell proliferation and suppresses apoptosis in human odontoblast-like cells.

• 出版日期2015-2-1