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Bone morphogenetic protein (BMP)1-3 enhances bone repair

Grgurevic, Lovorka, Macek, Boris, Mercep, Mladen, Jelic, Mislav, Smoljanovic, Tomislav, Erjavec, Igor, Dumic-Cule, Ivo, Prgomet, Stefan, Durdevic, Dragan, Vnuk, Drazen, Lipar, Marija, Stejskal, Marko, Kufner, Vera, Brkljacic, Jelena, Maticic, Drazen, Vukicevic, Slobodan
Biochemical and biophysical research communications 2011 v.408 no.1 pp. 25-31
biomarkers, bone marrow, bone morphogenetic proteins, collagen, extracellular matrix, genes, humans, metalloproteinases, mineralization, morphogenesis, neutralization, osteocalcin, patients, polyclonal antibodies, rabbits, rats, stem cells, transforming growth factor beta, ulna
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.