title: Wnt16 Signaling Is Required for IL-1β-Induced Matrix Metalloproteinase-13-Regulated Proliferation of Human Stem Cell-Derived Osteoblastic Cells.
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.
authors: Department of Endodontics, School of Dentistry, Aichi Gakuin University, Nagoya, Aichi 464-8651, Japan. ozeki@g.agu.ac.jp.
authors: Nobuaki
authors: N
authors: Ozeki
authors: Department of Medicinal Biochemistry, School of Pharmacy, Aichi Gakuin University, Nagoya, Aichi 464-8650, Japan. makio@dpc.agu.ac.jp.
authors: Makio
authors: M
authors: Mogi
authors: Department of Endodontics, School of Dentistry, Aichi Gakuin University, Nagoya, Aichi 464-8651, Japan. hanako@dpc.agu.ac.jp.
authors: Naoko
authors: N
authors: Hase
authors: Department of Endodontics, School of Dentistry, Aichi Gakuin University, Nagoya, Aichi 464-8651, Japan.
authors: Taiki
authors: T
authors: Hiyama
authors: Department of Endodontics, School of Dentistry, Aichi Gakuin University, Nagoya, Aichi 464-8651, Japan. ag123d27@dpc.agu.ac.jp.
authors: Hideyuki
authors: H
authors: Yamaguchi
authors: Department of Endodontics, School of Dentistry, Aichi Gakuin University, Nagoya, Aichi 464-8651, Japan. riechan@dpc.agu.ac.jp.
authors: Rie
authors: R
authors: Kawai
authors: Department of Medicinal Biochemistry, School of Pharmacy, Aichi Gakuin University, Nagoya, Aichi 464-8650, Japan. ayami@dpc.agu.ac.jp.
authors: Ayami
authors: A
authors: Kondo
authors: Department of Endodontics, School of Dentistry, Aichi Gakuin University, Nagoya, Aichi 464-8651, Japan. kazukun@dpc.agu.ac.jp.
authors: Kazuhiko
authors: K
authors: Nakata
mesh_terms: D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects; D051157:Frizzled Receptors / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D020868:Gene Silencing; D006801:Humans; D039001:Integrin alpha Chains / Q000235:genetics / Q000378:metabolism; D053583:Interleukin-1beta / Q000187:drug effects / Q000378:metabolism*; D060492:Low Density Lipoprotein Receptor-Related Protein-5 / Q000235:genetics / Q000378:metabolism; D053509:Matrix Metalloproteinase 13 / Q000235:genetics / Q000378:metabolism*; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects; D013234:Stem Cells / Q000166:cytology; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D015703:Antigens, CD; C489742:FZD2 protein, human; D051157:Frizzled Receptors; D039001:Integrin alpha Chains; D053583:Interleukin-1beta; D060492:Low Density Lipoprotein Receptor-Related Protein-5; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C417262:WNT16 protein, human; D051153:Wnt Proteins; C085725:integrin alpha7; D053509:Matrix Metalloproteinase 13
keywords: Wnt16; cell proliferation; interleukin-1β; matrix metalloproteinase; osteoblast