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

被引:69
作者
Grgurevic, Lovorka [1 ]
Macek, Boris [2 ]
Mercep, Mladen [3 ]
Jelic, Mislav [1 ]
Smoljanovic, Tomislav [1 ]
Erjavec, Igor [1 ]
Dumic-Cule, Ivo [1 ]
Prgomet, Stefan [1 ]
Durdevic, Dragan [4 ]
Vnuk, Drazen [5 ]
Lipar, Marija [5 ]
Stejskal, Marko [5 ]
Kufner, Vera [1 ]
Brkljacic, Jelena [1 ]
Maticic, Drazen [5 ]
Vukicevic, Slobodan [1 ]
机构
[1] Univ Zagreb, Lab Mineralized Tissues, Ctr Translat & Clin Res & Orthopaed Surg, Zagreb 10000, Croatia
[2] Univ Tubingen, Proteome Ctr, Interdept Inst Cell Biol, Tubingen, Germany
[3] Res Ctr Zagreb Ltd, GlaxoSmithKline, Zagreb, Croatia
[4] Clin Traumatol, Zagreb 10000, Croatia
[5] Univ Zagreb, Clin Surg Orthopaed & Ophthalmol, Fac Vet Med, Zagreb 10000, Croatia
关键词
BMP1-3; Bone fracture; ECM; BMP7; Differentiation; EXPRESSION; MATRIX;
D O I
10.1016/j.bbrc.2011.03.109
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 TGF beta, 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. In vitro BMP1-3 increased the expression of collagen type land 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. (C) 2011 Elsevier Inc. All rights reserved.
引用
收藏
页码:26 / +
页数:7
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