title: IL-1β-induced matrix metalloproteinase-13 is activated by a disintegrin and metalloprotease-28-regulated proliferation of human osteoblast-like cells.
abstract: We reported previously that matrix metalloproteinase (MMP)-13 accelerates bone remodeling in oral periradicular lesions, and indicated a potentially unique role for MMP-13 in wound healing and regeneration of alveolar bone. The ADAM (a disintegrin and metalloprotease) family is a set of multifunctional cell surface and secreted glycoproteins, of which ADAM-28 has been localized in bone and bone-like tissues. In this study, we show that interleukin (IL)-1β induces the expression of MMP-13 and ADAM-28 in homogeneous α7 integrin-positive human skeletal muscle stem cell (α7(+)hSMSC)-derived osteoblast-like (α7(+)hSMSC-OB) cells, and promotes proliferation while inhibiting apoptosis in these cells. At higher concentrations, however, IL-1β failed to induce the expression of these genes and caused an increase in apoptosis. We further employed ADAM-28 small interfering RNA (siRNA) to investigate whether IL-1β-induced MMP-13 expression is linked to this IL-1β-mediated changes in cell proliferation and apoptosis. Silencing ADAM-28 expression potently suppressed IL-1β-induced MMP-13 expression and activity, decreased cell proliferation and increased apoptosis in α7(+)hSMSC-OB cells. In contrast, MMP-13 siRNA had no effect on ADAM-28 expression, suggesting ADAM-28 regulates MMP-13. Exogenous MMP-13 induced α7(+)hSMSC-OB cell proliferation and could rescue ADAM-28 siRNA-induced apoptosis, and we found that proMMP-13 is partially cleaved into its active form by ADAM-28 in vitro. Overall, our results suggest that IL-1β-induced MMP-13 expression and changes in cell proliferation and apoptosis in α7(+)hSMSC-OB cells are regulated by ADAM-28.
authors.affiliation: Department of Endodontics, School of Dentistry, Aichi Gakuin University, 2-11 Suemori-dori, Chikusa-ku, Nagoya, Aichi 464-8651, Japan.
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Ozeki
authors.affiliation: Department of Endodontics, School of Dentistry, Aichi Gakuin University, 2-11 Suemori-dori, Chikusa-ku, Nagoya, Aichi 464-8651, Japan.
authors.forename: Rie
authors.initials: R
authors.lastname: Kawai
authors.affiliation: Department of Endodontics, School of Dentistry, Aichi Gakuin University, 2-11 Suemori-dori, Chikusa-ku, Nagoya, Aichi 464-8651, Japan.
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Yamaguchi
authors.affiliation: Department of Endodontics, School of Dentistry, Aichi Gakuin University, 2-11 Suemori-dori, Chikusa-ku, Nagoya, Aichi 464-8651, Japan.
authors.forename: Taiki
authors.initials: T
authors.lastname: Hiyama
authors.affiliation: Department of Endodontics, School of Dentistry, Aichi Gakuin University, 2-11 Suemori-dori, Chikusa-ku, Nagoya, Aichi 464-8651, Japan.
authors.forename: Katsue
authors.initials: K
authors.lastname: Kinoshita
authors.affiliation: Department of Endodontics, School of Dentistry, Aichi Gakuin University, 2-11 Suemori-dori, Chikusa-ku, Nagoya, Aichi 464-8651, Japan.
authors.forename: Naoko
authors.initials: N
authors.lastname: Hase
authors.affiliation: Department of Endodontics, School of Dentistry, Aichi Gakuin University, 2-11 Suemori-dori, Chikusa-ku, Nagoya, Aichi 464-8651, Japan.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Nakata
authors.affiliation: Department of Medicinal Biochemistry, School of Pharmacy, Aichi Gakuin University, 1-100 Kusumoto, Chikusa-ku, Nagoya, Aichi 464-8650, Japan.
authors.forename: Ayami
authors.initials: A
authors.lastname: Kondo
authors.affiliation: Department of Medicinal Biochemistry, School of Pharmacy, Aichi Gakuin University, 1-100 Kusumoto, Chikusa-ku, Nagoya, Aichi 464-8650, Japan. Electronic address: makio@dpc.agu.ac.jp.
authors.forename: Makio
authors.initials: M
authors.lastname: Mogi
authors.affiliation: Department of Endodontics, School of Dentistry, Aichi Gakuin University, 2-11 Suemori-dori, Chikusa-ku, Nagoya, Aichi 464-8651, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nakamura
mesh_terms: D016475:3T3 Cells; D051722:ADAM Proteins / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D017209:Apoptosis / Q000235:genetics*; D002460:Cell Line; D049109:Cell Proliferation; D053938:DNA Fragmentation; D019483:Disintegrins / Q000494:pharmacology; D006801:Humans; D039001:Integrin alpha Chains / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism*; D020781:Matrix Metalloproteinase 1 / Q000235:genetics; D053509:Matrix Metalloproteinase 13 / Q000235:genetics / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D018482:Muscle, Skeletal / Q000166:cytology; D010006:Osteoblasts / Q000187:drug effects / Q000378:metabolism; D010975:Platelet Aggregation Inhibitors / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering; D013234:Stem Cells
chemical_list: D015703:Antigens, CD; D019483:Disintegrins; D039001:Integrin alpha Chains; D053583:Interleukin-1beta; D008562:Membrane Glycoproteins; D010975:Platelet Aggregation Inhibitors; D034741:RNA, Small Interfering; C085725:integrin alpha7; D051722:ADAM Proteins; C410224:ADAM28 protein, human; C507079:MMP13 protein, human; D053509:Matrix Metalloproteinase 13; C522360:MMP1 protein, human; D020781:Matrix Metalloproteinase 1
keywords: A disintegrin and metalloprotease; Cell proliferation; Interleukin-1β; Matrix metalloproteinase; Osteoblast