title: Involvement of multiple CCN family members in platelets that support regeneration of joint tissues.
abstract: OBJECTIVE
  Platelet-rich plasma (PRP) has been widely used to enhance the regeneration of damaged joint tissues, such as osteoarthritic and rheumatoid arthritic cartilage. The aim of this study is to clarify the involvement of all of the CCN family proteins that are crucially associated with joint tissue regeneration.
  
  
  METHODS
  Cyr61-CTGF-NOV (CCN) family proteins in human platelets and megakaryocytic cells were comprehensively analyzed by Western blotting analysis. Production of CCN family proteins in megakaryocytes in vivo was confirmed by immunofluorescence analysis of mouse bone marrow cells. Effects of CCN family proteins found in platelets on chondrocytes were evaluated by using human chondrocytic HCS-2/8 cells.
  
  
  RESULTS
  Inclusion of CCN2, a mesenchymal tissue regenerator, was confirmed. Of note, CCN3, which counteracts CCN2, was newly found to be encapsulated in platelets. Interestingly, these two family members were not detectable in megakaryocytic cells, but their external origins were suggested. Furthermore, we found for the first time CCN5 and CCN1 that inhibits ADAMTS4 in both platelets and megakaryocytes. Finally, application of a CCN family cocktail mimicking platelets onto HCS-2/8 cells enhanced their chondrocytic phenotype.
  
  
  CONCLUSIONS
  Multiple inclusion of CCN1, 2 and 3 in platelets was clarified, which supports the harmonized regenerative potential of PRP in joint therapeutics.
authors.affiliation: a Department of Biochemistry and Molecular Dentistry , and.|b Department of Orthodontics , Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences , Okayama , Japan.
authors.forename: Chikako
authors.initials: C
authors.lastname: Hara
authors.affiliation: a Department of Biochemistry and Molecular Dentistry , and.|c Advanced Research Center for Oral and Craniofacial Sciences , Okayama University Dental School , Okayama , Japan , and.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kubota
authors.affiliation: a Department of Biochemistry and Molecular Dentistry , and.
authors.forename: Takashi
authors.initials: T
authors.lastname: Nishida
authors.affiliation: d Department of Membrane Biochemistry , Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences , Okayama , Japan.
authors.forename: Miki
authors.initials: M
authors.lastname: Hiasa
authors.affiliation: a Department of Biochemistry and Molecular Dentistry , and.
authors.forename: Takako
authors.initials: T
authors.lastname: Hattori
authors.affiliation: c Advanced Research Center for Oral and Craniofacial Sciences , Okayama University Dental School , Okayama , Japan , and.
authors.forename: Eriko
authors.initials: E
authors.lastname: Aoyama
authors.affiliation: d Department of Membrane Biochemistry , Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences , Okayama , Japan.
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Moriyama
authors.affiliation: b Department of Orthodontics , Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences , Okayama , Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kamioka
authors.affiliation: a Department of Biochemistry and Molecular Dentistry , and.|c Advanced Research Center for Oral and Craniofacial Sciences , Okayama University Dental School , Okayama , Japan , and.
authors.forename: Masaharu
authors.initials: M
authors.lastname: Takigawa
mesh_terms: D000818:Animals; D001792:Blood Platelets / Q000378:metabolism*; D055511:CCN Intercellular Signaling Proteins / Q000235:genetics / Q000378:metabolism*; D002356:Cartilage / Q000378:metabolism* / Q000502:physiology; D002460:Cell Line; D002478:Cells, Cultured; D006801:Humans; D051379:Mice; D053657:Platelet-Rich Plasma / Q000378:metabolism; D012038:Regeneration
chemical_list: D055511:CCN Intercellular Signaling Proteins
keywords: CCN family; Cartilage; Megakaryocyte; Platelet; Regeneration