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

Author:
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
Source:
Biochemical and biophysical research communications 2011 v.408 no.1 pp. 25-31
ISSN:
0006-291X
Subject:
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
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.
Agid:
893846