title: Bone morphogenetic protein (BMP)1-3 enhances bone repair.
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-E(1) 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.
authors: Laboratory for Mineralized Tissues, Center for Translational and Clinical Research and Orthopaedic Surgery, University of Zagreb, 10000 Zagreb, Croatia.
authors: Lovorka
authors: L
authors: Grgurevic
authors: Boris
authors: B
authors: Macek
authors: Mladen
authors: M
authors: Mercep
authors: Mislav
authors: M
authors: Jelic
authors: Tomislav
authors: T
authors: Smoljanovic
authors: Igor
authors: I
authors: Erjavec
authors: Ivo
authors: I
authors: Dumic-Cule
authors: Stefan
authors: S
authors: Prgomet
authors: Dragan
authors: D
authors: Durdevic
authors: Drazen
authors: D
authors: Vnuk
authors: Marija
authors: M
authors: Lipar
authors: Marko
authors: M
authors: Stejskal
authors: Vera
authors: V
authors: Kufner
authors: Jelena
authors: J
authors: Brkljacic
authors: Drazen
authors: D
authors: Maticic
authors: Slobodan
authors: S
authors: Vukicevic
mesh_terms: D000818:Animals; D055395:Bone Morphogenetic Protein 1 / Q000235:genetics / Q000494:pharmacology* / Q000502:physiology*; D001842:Bone and Bones / Q000187:drug effects* / Q000293:injuries / Q000502:physiology*; D002454:Cell Differentiation / Q000235:genetics; D002460:Cell Line; D024042:Collagen Type I / Q000378:metabolism; D050723:Fractures, Bone / Q000097:blood / Q000503:physiopathology*; D006801:Humans; D008297:Male; D051379:Mice; D010006:Osteoblasts / Q000166:cytology / Q000502:physiology; D010012:Osteogenesis / Q000235:genetics / Q000502:physiology; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000235:genetics / Q000494:pharmacology; D014945:Wound Healing / Q000187:drug effects / Q000502:physiology*
chemical_list: D024042:Collagen Type I; D011994:Recombinant Proteins; C525705:BMP1 protein, human; D055395:Bone Morphogenetic Protein 1