title: Bone Morphogenetic Proteins and myostatin pathways: key mediator of human sarcopenia.
abstract: Sarcopenia, osteoporosis and osteoarthritis are the most frequent musculoskeletal disorders affecting older people. The main aim of this study was to test the hypothesis that the balance between BMPs and myostatin pathways regulates the age-related muscle degeneration in OP and OA patients. To this end, we investigated the relationship among the expression of BMP-2/4-7, myostatin and phosphorylated Smads1-5-8 and the muscle quality, evaluated in term of fibers atrophy and satellite cells activity.
  
  
  
  In this retrospective study, we collected 123 biopsies of vastus lateralis: 48 biopsies from patients who underwent hip arthroplasty for subcapital fractures of the femur (OP), 55 biopsies from patients who underwent hip arthroplasty for osteoarthritis (OA) and 20 biopsies from patients who underwent hip arthroplasty for high-energy hip fractures (CTRL). Muscle biopsies were fixed in 4% paraformaldehyde and paraffin embedded. Serial sections were used for morphometrical and immunohistochemical analysis (BMP/2/4-7, myostatin, Smads1-5-8, Pax7 and myogenin). In addition, 1 mm3of muscle tissue of each patient was embedded in epon for ultrastructural study.
  
  
  
  Morphometric data indicated an increase of the number of atrophic fibers in OP patients compare to OA. In line with these data, we found an high regenerative potential in muscle tissues of OA patients due to the significant amount of both Pax7 and myogenin positive satellite cells detected in OA group. In addition, our data showed the decrease of BMP2/4 and -7 expression in OP patients compared to both OA group and CTRL. Conversely, OP patients were characterized by high levels of myostatin expression. A different expression profile was also found for phosphorylated Smad1-5-8 between OP and OA patients. In particular, OP patients showed a low number of positive phosphorylated Smad1-5-8 nuclei.
  
  
  
  The identification of molecular pathways involved in the pathogenesis of sarcopenia open new prospective for the development of drugs able to prevent/treat the muscle impairment that occur in elderly. Results here reported, highlighting the role of BMPs and myostatin pathways in physio-pathogenesis of human sarcopenia, allow us to propose human recombinant BMP-2/7 and anti-myostatin antibodies as a possible therapeutic option for the sarcopenia.
authors.affiliation: Multidisciplinary Study of the Effects of Microgravity on Bone Cells" Project, Spatial Biomedicine Center, Italian Space Agency (ASI), Via del Politecnico snc, 00133, Rome, Italy.|Anatomic Pathology Section, Department of Experimental Medicine and Surgery, University of Rome 'Tor Vergata', Via Montpellier 1, 00133, Rome, Italy.
authors.forename: Manuel
authors.initials: M
authors.lastname: Scimeca
authors.affiliation: Department of Orthopedics and Traumatology, "Policlinico Tor Vergata" Foundation, Viale Oxford 1, 00133, Rome, Italy.
authors.forename: Eleonora
authors.initials: E
authors.lastname: Piccirilli
authors.affiliation: Department of Biomedicine and Prevention, University of Rome 'Tor Vergata', Via Montpellier 1, 00133, Rome, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Mastrangeli
authors.affiliation: Department of Orthopedics and Traumatology, "Policlinico Tor Vergata" Foundation, Viale Oxford 1, 00133, Rome, Italy.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Rao
authors.affiliation: Department of Orthopedics and Traumatology, "Policlinico Tor Vergata" Foundation, Viale Oxford 1, 00133, Rome, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Feola
authors.affiliation: Department of Biomedicine and Prevention, University of Rome 'Tor Vergata', Via Montpellier 1, 00133, Rome, Italy.
authors.forename: Augusto
authors.initials: A
authors.lastname: Orlandi
authors.affiliation: Department of Orthopedics and Traumatology, "Policlinico Tor Vergata" Foundation, Viale Oxford 1, 00133, Rome, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Gasbarra
authors.affiliation: Anatomic Pathology Section, Department of Experimental Medicine and Surgery, University of Rome 'Tor Vergata', Via Montpellier 1, 00133, Rome, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Bonanno
authors.affiliation: Department of Orthopedics and Traumatology, "Policlinico Tor Vergata" Foundation, Viale Oxford 1, 00133, Rome, Italy. umberto.tarantino@uniroma2.it.|Department of Clinical Sciences and Translational Medicine, University of Rome Tor Vergata, Via Montpellier 1, 00133, Rome, Italy. umberto.tarantino@uniroma2.it.
authors.forename: Umberto
authors.initials: U
authors.lastname: Tarantino
mesh_terms: D019485:Bone Morphogenetic Proteins / Q000378:metabolism*; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D018485:Muscle Fibers, Skeletal / Q000473:pathology / Q000648:ultrastructure; D055435:Myostatin / Q000378:metabolism*; D010766:Phosphorylation; D055948:Sarcopenia / Q000378:metabolism*; D032496:Satellite Cells, Skeletal Muscle / Q000473:pathology / Q000648:ultrastructure; D051785:Smad Proteins / Q000378:metabolism
chemical_list: D019485:Bone Morphogenetic Proteins; D055435:Myostatin; D051785:Smad Proteins