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Int. J. Mol. Sci. 2016, 17(2), 221; doi:10.3390/ijms17020221

Wnt16 Signaling Is Required for IL-1β-Induced Matrix Metalloproteinase-13-Regulated Proliferation of Human Stem Cell-Derived Osteoblastic Cells

1
Department of Endodontics, School of Dentistry, Aichi Gakuin University, Nagoya, Aichi 464-8651, Japan
2
Department of Medicinal Biochemistry, School of Pharmacy, Aichi Gakuin University, Nagoya, Aichi 464-8650, Japan
*
Author to whom correspondence should be addressed.
Academic Editor: Wenbin Deng
Received: 7 January 2016 / Revised: 1 February 2016 / Accepted: 1 February 2016 / Published: 6 February 2016
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Abstract

We established a differentiation method for homogeneous α7 integrin-positive human skeletal muscle stem cell (α7+hSMSC)-derived osteoblast-like (α7+hSMSC-OB) cells, and found that interleukin (IL)-1β induces matrix metalloproteinase (MMP)-13-regulated proliferation of these cells. These data suggest that MMP-13 plays a potentially unique physiological role in the regeneration of osteoblast-like cells. Here, we examined whether up-regulation of MMP-13 activity by IL-1β was mediated by Wingless/int1 (Wnt) signaling and increased the proliferation of osteoblast-like cells. IL-1β increased the mRNA and protein levels of Wnt16 and the Wnt receptor Lrp5/Fzd2. Exogenous Wnt16 was found to increase MMP-13 mRNA, protein and activity, and interestingly, the proliferation rate of these cells. Treatment with small interfering RNAs against Wnt16 and Lrp5 suppressed the IL-1β-induced increase in cell proliferation. We revealed that a unique signaling cascade IL-1β→Wnt16→Lrp5→MMP-13, was intimately involved in the proliferation of osteoblast-like cells, and suggest that IL-1β-induced MMP-13 expression and changes in cell proliferation are regulated by Wnt16. View Full-Text
Keywords: Wnt16; matrix metalloproteinase; osteoblast; interleukin-1β; cell proliferation Wnt16; matrix metalloproteinase; osteoblast; interleukin-1β; cell proliferation
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Ozeki, N.; Mogi, M.; Hase, N.; Hiyama, T.; Yamaguchi, H.; Kawai, R.; Kondo, A.; Nakata, K. Wnt16 Signaling Is Required for IL-1β-Induced Matrix Metalloproteinase-13-Regulated Proliferation of Human Stem Cell-Derived Osteoblastic Cells. Int. J. Mol. Sci. 2016, 17, 221.

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