title: Magnesium enhances adherence and cartilage formation of synovial mesenchymal stem cells through integrins.
abstract: OBJECTIVE
  We previously reported that more than 60% of synovial mesenchymal stem cells (MSCs) placed on osteochondral defects adhered to the defect within 10 min and promoted cartilage regeneration. The efficiency of adherence is considered to depend on the interaction between cells and extracellular matrix (ECM), in which integrins may play some important roles. Divalent cations such as calcium, magnesium, and manganese may affect functions of integrins, and the integrins may be involved in differentiation of MSCs. Among divalent cations, magnesium is used in clinical practice as a therapeutic agent and increases the affinity of integrin to ECM. In this study, we investigated whether magnesium enhanced adherence and chondrogenesis of synovial MSC through integrins.
  
  
  METHODS
  We performed assays for adherence of human synovial MSCs to collagen-coated slides, in vitro chondrogenesis, ex vivo assays for adherence of human synovial MSCs to osteochondral defect, and in vivo assays for adherence and cartilage formation of synovial MSCs in a rabbit osteochondral defect model.
  
  
  RESULTS
  Magnesium increased adhesion of human synovial MSCs to collagen, and this effect was inhibited by neutralizing antibodies for integrin α3 and β1. Magnesium also promoted synthesis of cartilage matrix during in vitro chondrogenesis of synovial MSCs, which was diminished by neutralizing antibodies for integrin β1 but not for integrin α3. Ex vivo analyses demonstrated that magnesium enhanced adherence of human synovial MSCs to osteochondral defects. In vivo studies in rabbits showed that magnesium promoted adherence at 1 day and cartilage formation of synovial MSCs at 2 weeks.
  
  
  CONCLUSIONS
  Magnesium enhanced adherence of synovial MSCs through integrins, which promoted synthesis of cartilage matrix at an early phase.
authors.affiliation: Section of Orthopedic Surgery, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan. shimaya.orj@tmd.ac.jp
authors.forename: M
authors.initials: M
authors.lastname: Shimaya
authors.forename: T
authors.initials: T
authors.lastname: Muneta
authors.forename: S
authors.initials: S
authors.lastname: Ichinose
authors.forename: K
authors.initials: K
authors.lastname: Tsuji
authors.forename: I
authors.initials: I
authors.lastname: Sekiya
mesh_terms: D000328:Adult; D000818:Animals; D002358:Cartilage, Articular / Q000502:physiology; D002448:Cell Adhesion / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D020219:Chondrogenesis / Q000187:drug effects*; D005260:Female; D006801:Humans; D039422:Integrin alpha3 / Q000502:physiology; D019012:Integrin beta1 / Q000502:physiology; D016023:Integrins / Q000502:physiology*; D008274:Magnesium / Q000494:pharmacology*; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D011817:Rabbits; D012038:Regeneration; D013583:Synovial Membrane / Q000166:cytology / Q000187:drug effects*
chemical_list: D039422:Integrin alpha3; D019012:Integrin beta1; D016023:Integrins; D008274:Magnesium