title: Hepatocyte growth factor and alternative splice variants - expression, regulation and implications in osteogenesis and bone health and repair.
abstract: BACKGROUND
  Bone marrow-derived mesenchymal stem cells (MSCs) can differentiate into multiple cell types, including osteoblasts, chondrocytes, and adipocytes. These pluripotent cells secrete hepatocyte growth factor (HGF), which regulates cell growth, survival, motility, migration, mitogenesis and is important for tissue development/regeneration. HGF has four splice variants, NK1, NK2, NK3, and NK4 which have varying functions and affinities for the HGF receptor, cMET. HGF promotes osteoblastic differentiation of MSCs into bone forming cells, playing a role in bone development, health and repair.
  
  
  METHODS
  This review will focus on the effects of HGF in osteogenesis, bone repair and bone health, including structural and functional insights into the role of HGF in the body.
  
  
  CONCLUSIONS
  Approximately 6.2 million Americans experience a fracture annually, with 5-10% being mal- or non-union fractures. HGF is important in priming MSCs for osteogenic differentiation in vitro and is currently being studied to assess its role during bone repair in vivo. Due to the high turnover rate of systemic HGF, non-classic modes of HGF-treatment, including naked-plasmid HGF delivery and the use of HGF splice variants (NK1 & NK2) are being studied to find safe and efficacious treatments for bone disorders, such as mal- or non-union fractures.
authors.affiliation: a Geriatric Research, Education, and Clinical Center, and Research Service , Bruce W. Carter Veterans Affairs Medical Center , Miami , FL , USA.
authors.forename: Rachel N
authors.initials: RN
authors.lastname: Frisch
authors.affiliation: a Geriatric Research, Education, and Clinical Center, and Research Service , Bruce W. Carter Veterans Affairs Medical Center , Miami , FL , USA.|b Biochemistry & Molecular Biology , University of Miami Miller School of Medicine , Miami , FL , USA.
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Curtis
authors.affiliation: a Geriatric Research, Education, and Clinical Center, and Research Service , Bruce W. Carter Veterans Affairs Medical Center , Miami , FL , USA.
authors.forename: Kristina K
authors.initials: KK
authors.lastname: Aenlle
authors.affiliation: a Geriatric Research, Education, and Clinical Center, and Research Service , Bruce W. Carter Veterans Affairs Medical Center , Miami , FL , USA.|b Biochemistry & Molecular Biology , University of Miami Miller School of Medicine , Miami , FL , USA.|c Medicine , University of Miami Miller School of Medicine , Miami , FL , USA.
authors.forename: Guy A
authors.initials: GA
authors.lastname: Howard
mesh_terms: D017667:Adipocytes / Q000166:cytology; D017398:Alternative Splicing / Q000235:genetics; D000818:Animals; D001842:Bone and Bones / Q000378:metabolism*; D002454:Cell Differentiation; D019902:Chondrocytes / Q000166:cytology; D005786:Gene Expression Regulation; D017228:Hepatocyte Growth Factor / Q000008:administration & dosage / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology; D010006:Osteoblasts / Q000166:cytology; D010012:Osteogenesis / Q000235:genetics*
chemical_list: D017228:Hepatocyte Growth Factor
keywords: Bone; HGF; Hepatocyte Growth Factor; Osteoblastic Differentiation; Osteoblasts; Osteoclasts; cMET