title: Key role of the expression of bone morphogenetic proteins in increasing the osteogenic activity of osteoblast-like cells exposed to shock waves and seeded on bioactive glass-ceramic scaffolds for bone tissue engineering.
abstract: In this work, the role of shock wave-induced increase of bone morphogenetic proteins in modulating the osteogenic properties of osteoblast-like cells seeded on a bioactive scaffold was investigated using gremlin as a bone morphogenetic protein antagonist. Bone-like glass-ceramic scaffolds, based on a silicate experimental bioactive glass developed at the Politecnico di Torino, were produced by the sponge replication method and used as porous substrates for cell culture. Human MG-63 cells, exposed to shock waves and seeded on the scaffolds, were treated with gremlin every two days and analysed after 20 days for the expression of osteoblast differentiation markers. Shock waves have been shown to induce osteogenic activity mediated by increased expression of alkaline phosphatase, osteocalcin, type I collagen, BMP-4 and BMP-7. Cells exposed to shock waves plus gremlin showed increased growth in comparison with cells treated with shock waves alone and, conversely, mRNA contents of alkaline phosphatase and osteocalcin were significantly lower. Therefore, the shock wave-mediated increased expression of bone morphogenetic protein in MG-63 cells seeded on the scaffolds is essential in improving osteogenic activity; blocking bone morphogenetic protein via gremlin completely prevents the increase of alkaline phosphatase and osteocalcin. The results confirmed that the combination of glass-ceramic scaffolds and shock waves exposure could be used to significantly improve osteogenesis opening new perspectives for bone regenerative medicine.
authors.affiliation: Department of Clinical and Biological Sciences, University of Turin, Turin, Italy.
authors.forename: Giuliana
authors.initials: G
authors.lastname: Muzio
authors.affiliation: Department of Clinical and Biological Sciences, University of Turin, Turin, Italy.
authors.forename: Germana
authors.initials: G
authors.lastname: Martinasso
authors.affiliation: Institute of Materials Physics and Engineering, Department of Applied Science and Technology, Politecnico di Torino, Turin, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Baino
authors.affiliation: Department of Medical Sciences, University of Turin, Turin, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Frairia
authors.affiliation: Institute of Materials Physics and Engineering, Department of Applied Science and Technology, Politecnico di Torino, Turin, Italy chiara.vitale@polito.it.
authors.forename: Chiara
authors.initials: C
authors.lastname: Vitale-Brovarone
authors.affiliation: Department of Clinical and Biological Sciences, University of Turin, Turin, Italy.
authors.forename: Rosa A
authors.initials: RA
authors.lastname: Canuto
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D019485:Bone Morphogenetic Proteins / Q000378:metabolism*; D001861:Bone Regeneration; D001842:Bone and Bones / Q000473:pathology; D049109:Cell Proliferation; D002516:Ceramics / Q000737:chemistry*; D005786:Gene Expression Regulation; D006801:Humans; D008422:Materials Testing; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism*; D015675:Osteocalcin / Q000737:chemistry; D010012:Osteogenesis / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds / Q000737:chemistry*; D055114:X-Ray Microtomography
chemical_list: D019485:Bone Morphogenetic Proteins; D012333:RNA, Messenger; D015675:Osteocalcin; C023506:Glass ceramics; D000469:Alkaline Phosphatase
keywords: Scaffold; bone morphogenetic proteins; bone tissue engineering; gremlin; shock waves