Plant-derived soybean peroxidase stimulates osteoblast collagen biosynthesis, matrix mineralization, and accelerates bone regeneration in a sheep model
Alexandra J. Barker,
Agnes Arthur,
Mark O. DeNichilo,
Romana Panagopoulos,
Stan Gronthos,
Peter J. Anderson,
Andrew C.W. Zannettino,
Andreas Evdokiou,
Vasilios Panagopoulos
Affiliations
Alexandra J. Barker
Musculoskeletal Biology Research Laboratory, Clinical and Health Sciences, University of South Australia, Adelaide, Australia
Agnes Arthur
Mesenchymal Stem Cell Laboratory, Adelaide Medical School, Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, Australia; Precision Medicine Theme, South Australian Health and Medical Research Institute, Adelaide, Australia
Mark O. DeNichilo
Centre for Cancer Biology, University of South Australia, Adelaide, Australia
Romana Panagopoulos
Breast Cancer Research Unit, School of Medicine, Discipline of Surgery and Orthopaedics, Basil Hetzel Institute, University of Adelaide, Adelaide, Australia
Stan Gronthos
Mesenchymal Stem Cell Laboratory, Adelaide Medical School, Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, Australia; Precision Medicine Theme, South Australian Health and Medical Research Institute, Adelaide, Australia
Peter J. Anderson
Mesenchymal Stem Cell Laboratory, Adelaide Medical School, Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, Australia; Centre for Cancer Biology, University of South Australia, Adelaide, Australia; Australian Craniofacial Unit, Women's and Children's Hospital, Department of Paediatrics and Dentistry, University of Adelaide, Adelaide, Australia; Central Adelaide Local Health Network, Adelaide, Australia
Andrew C.W. Zannettino
Myeloma Research Laboratory, Adelaide Medical School, Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, Australia; Precision Medicine Theme, South Australian Health and Medical Research Institute, Adelaide, Australia; Department of Haematology, Royal Adelaide Hospital, Adelaide, Australia; Central Adelaide Local Health Network, Adelaide, Australia
Andreas Evdokiou
Breast Cancer Research Unit, School of Medicine, Discipline of Surgery and Orthopaedics, Basil Hetzel Institute, University of Adelaide, Adelaide, Australia
Vasilios Panagopoulos
Myeloma Research Laboratory, Adelaide Medical School, Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, Australia; Breast Cancer Research Unit, School of Medicine, Discipline of Surgery and Orthopaedics, Basil Hetzel Institute, University of Adelaide, Adelaide, Australia; Precision Medicine Theme, South Australian Health and Medical Research Institute, Adelaide, Australia; Corresponding author at: Myeloma Research Laboratory, Level 5 South, South Australian Health and Medical Research Institute, Adelaide SA 500, Australia.
Bone defects arising from fractures or disease represent a significant problem for surgeons to manage and are a substantial economic burden on the healthcare economy. Recent advances in the development of biomaterial substitutes provides an attractive alternative to the current “gold standard” autologous bone grafting. Despite on-going research, we are yet to identify cost effective biocompatible, osteo-inductive factors that stimulate controlled, accelerated bone regeneration.We have recently reported that enzymes with peroxidase activity possess previously unrecognised roles in extracellular matrix biosynthesis, angiogenesis and osteoclastogenesis, which are essential processes in bone remodelling and repair. Here, we report for the first time, that plant-derived soybean peroxidase (SBP) possesses pro-osteogenic ability by promoting collagen I biosynthesis and matrix mineralization of human osteoblasts in vitro. Mechanistically, SBP regulates osteogenic genes responsible for inflammation, extracellular matrix remodelling and ossification, which are necessary for normal bone healing. Furthermore, SBP was shown to have osteo-inductive properties, that when combined with commercially available biphasic calcium phosphate (BCP) granules can accelerate bone repair in a critical size long bone defect ovine model. Micro-CT analysis showed that SBP when combined with commercially available biphasic calcium phosphate (BCP) granules significantly increased bone formation within the defects as early as 4 weeks compared to BCP alone. Histomorphometric assessment demonstrated accelerated bone formation prominent at the defect margins and surrounding individual BCP granules, with evidence of intramembranous ossification. These results highlight the capacity of SBP to be an effective regulator of osteoblastic function and may be beneficial as a new and cost effective osteo-inductive agent to accelerate repair of large bone defects.
