title: Bone morphogenetic protein 2 stimulates chondrogenesis of equine synovial membrane-derived progenitor cells.
abstract: OBJECTIVE
  Bone morphogenetic protein 2 (BMP-2) is critical for skeletal and cartilage development, homeostasis and repair. This study was conducted to clone and characterize equine BMP-2, develop expression constructs for equine BMP-2, and to determine whether BMP-2 can stimulate chondrogenesis of equine synovial membrane-derived progenitor cells (SMPC).
  
  
  METHODS
  Equine BMP-2 cDNA was amplified from chondrocyte RNA, and then transferred into an expression plasmid and adenoviral vector. Effective expression of equine BMP-2 was confirmed using a BMP reporter cell line. SMPC were isolated from synovium, expanded through two passages and transferred to chondrogenic cultures, with recombinant human (rh) transforming growth factor beta 1 (TGF-β1) or rhBMP-2. Chondrogenesis was assessed by up-regulation of collagen types II and X, and aggrecan mRNA, secretion of collagen type II protein and sulfated glycosaminoglycans (sGAG), and by alkaline phosphatase induction. Chondrogenic stimulation of SMPC by the equine BMP-2 adenovirus was assessed by sGAG secretion and histology.
  
  
  RESULTS
  The mature equine BMP-2 peptide is identical to human and murine peptides. Recombinant human BMP-2 and TGF-β1 stimulated equivalent amounts of collagen type II protein in SMPC pellets, but sGAG secretion was doubled by BMP-2. Neither factor stimulated hypertrophic marker expression. The equine BMP-2 adenoviral vector induced chondrogenesis comparably to rhBMP-2 protein, with no indication of hypertrophy.
  
  
  CONCLUSIONS
  Bone morphogenetic protein 2 is a potent inducer of SMPC non-hypertrophic chondrogenesis, supporting the use of this combination for articular cartilage repair applications.
authors.forename: Yuwen
authors.initials: Y
authors.lastname: Chen
authors.forename: Evelyn
authors.initials: E
authors.lastname: Caporali
authors.affiliation: Dr. Matthew Stewart, University of Illinois at Urbana-Champaign, Veterinary Clinical Medicine, 1008 W Hazelwood Dr., Urbana, IL 61802, United States, Phone: +1 217 265 5026, E-mail: matt1@illinois.edu.
authors.forename: Matthew
authors.initials: M
authors.lastname: Stewart
mesh_terms: D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000494:pharmacology*; D002478:Cells, Cultured; D020219:Chondrogenesis / Q000187:drug effects*; D006736:Horses; D013234:Stem Cells / Q000187:drug effects* / Q000502:physiology; D013583:Synovial Membrane / Q000166:cytology / Q000187:drug effects*; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology
chemical_list: D055396:Bone Morphogenetic Protein 2; D053773:Transforming Growth Factor beta1
keywords: Equine BMP-2; adenoviral vector; bone morphogenetic protein 2; chondrogenesis; synovial membrane progenitor