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

Grgurević, Lovorka and Maček, Boris and Merčep, Mladen and Jelić, Mislav and Smoljanović, Tomislav and Erjavec, Igor and Dumić-Čule, Ivo and Prgomet, Stefan and Đurđević, Dragan and Vnuk, Dražen and Lipar, Marija and Stejskal, Marko and Kufner, Vera and Brkljačić, Jelena and Matičić, Dražen and Vukičević, Slobodan (2011) Bone morphogenetic protein (BMP)1-3 enhances bone repair. Biochemical and Biophysical Research Communications, 408 (1). pp. 25-31. ISSN 0006-291X

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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.

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