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

• Published in: International journal of molecular sciences 2016-02, Vol.17 (2), p.221-221
• Main Authors: Ozeki, Nobuaki, Mogi, Makio, Hase, Naoko, Hiyama, Taiki, Yamaguchi, Hideyuki, Kawai, Rie, Kondo, Ayami, Nakata, Kazuhiko
• Format: Article
• Language: English
• Subjects: Antigens, CD - genetics; Antigens, CD - metabolism; Cell Differentiation - genetics; cell proliferation; Cell Proliferation - drug effects; Frizzled Receptors - genetics; Frizzled Receptors - metabolism; Gene Expression Regulation - drug effects; Gene Silencing; Humans; Integrin alpha Chains - genetics; Integrin alpha Chains - metabolism; Interleukin-1beta - drug effects; Interleukin-1beta - metabolism; interleukin-1β; Low Density Lipoprotein Receptor-Related Protein-5 - genetics; Low Density Lipoprotein Receptor-Related Protein-5 - metabolism; matrix metalloproteinase; Matrix Metalloproteinase 13 - genetics; Matrix Metalloproteinase 13 - metabolism; osteoblast; Osteoblasts - cytology; Osteoblasts - drug effects; Osteoblasts - metabolism; RNA Interference; RNA, Messenger - genetics; RNA, Messenger - metabolism; RNA, Small Interfering - genetics; Signal Transduction - drug effects; Stem Cells - cytology; Wnt Proteins - genetics; Wnt Proteins - metabolism; Wnt16
• ISSN: 1422-0067; 1422-0067
• DOI: 10.3390/ijms17020221

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.