| Institution: | aLaboratory for Mineralized Tissues, Center for Translational and Clinical Research and Orthopaedic Surgery, University of Zagreb, 10000 Zagreb, Croatia;bProteome Center, Interdepartmental Institute for Cell Biology, University of Tuebingen, Tuebingen, Germany;cGlaxoSmithKline Research Center Zagreb Ltd., Zagreb, Croatia;dClinic of Traumatology, 10000 Zagreb, Croatia;eClinic for Surgery, Orthopaedics and Ophthalmology, Faculty of Veterinary Medicine, University of Zagreb, 10000 Zagreb, Croatia |
| Abstract: | Members of the astacin family of metalloproteinases such as human bone morphogenetic protein 1 (BMP-1) regulate morphogenesis by processing precursors to mature functional extracellular matrix (ECM) proteins and several growth factors including TGFβ, BMP2, BMP4 and GFD8. We have recently discovered that BMP1-3 isoform of the Bmp-1 gene circulates in the human plasma and is significantly increased in patients with acute bone fracture. We hypothesized that circulating BMP1-3 might have an important role in bone repair and serve as a novel bone biomarker. When administered systemically to rats with a long bone fracture and locally to rabbits with a critical size defect of the ulna, recombinant human BMP1-3 enhanced bone healing. In contrast, neutralization of the endogenous BMP1-3 by a specific polyclonal antibody delayed the bone union. Invitro BMP1-3 increased the expression of collagen type I and osteocalcin in MC3T3-E1 osteoblast like cells, and enhanced the formation of mineralized bone nodules from bone marrow mesenchymal stem cells. We suggest that BMP1-3 is a novel systemic regulator of bone repair. |
