title: The potential role of free chitosan in bone trauma and bone cancer management.
abstract: Bone defects caused by fractures or cancer-mediated destruction are debilitating. Chitosan is commonly used in scaffold matrices for bone healing, but rarely as a free drug. We demonstrate that free chitosan promotes osteoblast proliferation and osteogenesis in mesenchymal stem cells, increases osteopontin and collagen I expression, and reduces osteoclastogenesis. Chitosan inhibits invasion of endothelial cells, downregulating uPA/R, MT1-MMP, cdc42 and Rac1. Better healing of bone fractures with greater trabecular bone formation was observed in mice treated with chitosan. Chitosan induces apoptosis in osteotropic prostate and breast cancer cells via caspase-2 and -3 activation, and reduces their establishment in bone. Chitosan is pro-apoptotic in osteosarcoma cells, but not their normal counterpart, osteoblasts, or chondrosarcoma cells. Systemic delivery of chitosan does not perturb angiogenesis, bone volume or instinctive behaviour in pregnant mice, but decreases foetal length and changes pancreatic secretory acini. With certain controls in place, chitosan could be useful for bone trauma management.
authors.affiliation: Department of Orthopaedics, St Vincent's Health, University of Melbourne, Fitzroy 3065, Australia.
authors.forename: Mei L
authors.initials: ML
authors.lastname: Tan
authors.affiliation: Department of Orthopaedics, the First Affiliated Hospital with Nanjing Medical University, Nanjing 210029, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Shao
authors.affiliation: Department of Pathology, University of Melbourne, Parkville, VIC 3050, Australia.
authors.forename: Anna M
authors.initials: AM
authors.lastname: Friedhuber
authors.affiliation: College of Health and Biomedicine, Victoria University, St Albans, VIC 3021, Australia.
authors.forename: Mallory
authors.initials: M
authors.lastname: van Moorst
authors.affiliation: College of Health and Biomedicine, Victoria University, St Albans, VIC 3021, Australia.
authors.forename: Mina
authors.initials: M
authors.lastname: Elahy
authors.affiliation: College of Health and Biomedicine, Victoria University, St Albans, VIC 3021, Australia.
authors.forename: Sivanjah
authors.initials: S
authors.lastname: Indumathy
authors.affiliation: Department of Chemical and Biomolecular Engineering, University of Melbourne, Parkville, VIC 3050, Australia.
authors.forename: Dave E
authors.initials: DE
authors.lastname: Dunstan
authors.affiliation: Department of Orthopaedics, the First Affiliated Hospital with Nanjing Medical University, Nanjing 210029, China.
authors.forename: Yongzhong
authors.initials: Y
authors.lastname: Wei
authors.affiliation: School of Pharmacy, Curtin University, Bentley, WA 6102, Australia; Biosciences Research Precinct, Curtin University, Bentley, WA 6102, Australia. Electronic address: Crispin.Dass@curtin.edu.au.
authors.forename: Crispin R
authors.initials: CR
authors.lastname: Dass
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D001842:Bone and Bones / Q000187:drug effects / Q000473:pathology*; D053143:Caspase 2 / Q000378:metabolism; D045744:Cell Line, Tumor; D048271:Chitosan / Q000494:pharmacology / Q000627:therapeutic use*; D042783:Endothelial Cells / Q000187:drug effects / Q000473:pathology; D005260:Female; D005333:Fetus / Q000187:drug effects; D017102:Fracture Healing / Q000187:drug effects; D050723:Fractures, Bone / Q000188:drug therapy / Q000473:pathology; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000187:drug effects / Q000473:pathology; D008807:Mice, Inbred BALB C; D010006:Osteoblasts / Q000187:drug effects / Q000473:pathology; D010010:Osteoclasts / Q000187:drug effects / Q000473:pathology; D011247:Pregnancy; D051381:Rats; D014947:Wounds and Injuries / Q000188:drug therapy*
chemical_list: D048271:Chitosan; D053143:Caspase 2
keywords: Angiogenesis; Cancer; Chitosan; Fracture; Osteogenesis; Stem cell