title: Magnesium ions facilitate integrin alpha 2- and alpha 3-mediated proliferation and enhance alkaline phosphatase expression and activity in hBMSCs.
abstract: Magnesium metal and its alloys have been proposed as a novel class of bone implant biomaterials because of their biodegradability and mechanical properties. The purpose of this study was to determine whether magnesium ions, which are released abundantly from alloys, affect proliferation and differentiation of human bone marrow-derived stromal cells (hBMSCs). High levels of magnesium ions did not induce cytotoxicity in hBMSCs, but treatment with 2.5-10 mm magnesium ions for 48-72 h significantly increased hBMSC proliferation. The expression of integrins α2 and α3, but not β1, was upregulated compared with the control and shifted from α3 to α2 in hBMSCs treated with magnesium ions. Knockdown of integrins α2 and/or α3 significantly reduced magnesium-induced proliferation of hBMSCs. Magnesium exposure profoundly enhanced alkaline phosphatase (ALP) gene expression and activity even at a relatively low magnesium concentration (2.5 mm). Exposure to magnesium ions facilitated hBMSC proliferation via integrin α2 and α3 expression and partly promoted differentiation into osteoblasts via the alteration of ALP expression and activity. Accordingly, magnesium could be a useful biomaterial for orthopaedic applications such as bone implant biomaterials for repair and regeneration of bone defects in orthopaedic and dental fields. Copyright © 2014 John Wiley & Sons, Ltd.
authors.affiliation: Department of Pharmacy, College of Pharmacy, Dankook University, Cheonan-si, Chungnam, Korea.
authors.forename: Yea-Hyun
authors.initials: YH
authors.lastname: Leem
authors.affiliation: Department of Orthopedics, Seoul Asan Hospital, Seoul, Korea.
authors.forename: Kang-Sik
authors.initials: KS
authors.lastname: Lee
authors.affiliation: Department of Orthopedics, Seoul Asan Hospital, Seoul, Korea.
authors.forename: Jung-Hwa
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Biomaterial Research Center, Korea Institute of Science and Technology, Seongbuk-Gu, Seoul, Korea.
authors.forename: Hyun-Kwang
authors.initials: HK
authors.lastname: Seok
authors.affiliation: Department of Orthopedics, Seoul Asan Hospital, Seoul, Korea. jschang@amc.seoul.kr.
authors.forename: Jae-Suk
authors.initials: JS
authors.lastname: Chang
authors.affiliation: Department of Orthopedics, Seoul Asan Hospital, Seoul, Korea. osdlee@gmail.com.
authors.forename: Dong-Ho
authors.initials: DH
authors.lastname: Lee
mesh_terms: D000469:Alkaline Phosphatase / Q000096:biosynthesis*; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism*; D002413:Cations, Divalent / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D006801:Humans; D039421:Integrin alpha2 / Q000378:metabolism*; D039422:Integrin alpha3 / Q000378:metabolism*; D008274:Magnesium / Q000494:pharmacology*; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism; D017154:Stromal Cells / Q000166:cytology / Q000378:metabolism*
chemical_list: D002413:Cations, Divalent; D039421:Integrin alpha2; D039422:Integrin alpha3; D000469:Alkaline Phosphatase; D008274:Magnesium
keywords: RUNX2; alkaline phosphatase; biomaterial; integrin; magnesium; osteocalcin