title: BMP-6 and BMPR-1a are up-regulated in the growth plate of the fractured tibia.
abstract: Bone overgrowth is a known phenomenon occurring after fracture of growing long bones with possible long-term physical consequences for affected children. Here, the physeal expression of bone morphogenetic proteins (BMPs) was investigated in a fracture-animal model to test the hypothesis that a diaphyseal fracture stimulates the physeal expression of these known key regulators of bone formation, thus stimulating bone overgrowth. Sprague-Dawley rats (male, 4 weeks old), were subjected to a unilateral mid-diaphyseal tibial fracture. Kinetic expression of physeal BMP-2, -4, -6, -7, and BMP receptor-1a (BMPR-1a) was analyzed in a monthly period by quantitative real time-polymerase chain reaction and immunohistochemistry. On Days 1, 3, 10, and 14 post-fracture, no changes in physeal BMPs gene-expression were detected. Twenty-nine days post-fracture, when the fracture was consolidated, physeal expression of BMP-6 and BMPR-1a was significantly upregulated in the growth plate of the fractured and contra-lateral intact bone compared to control (p<0.005). This study demonstrates a late role of BMP-6 and BMPR-1a in fracture-induced physeal growth alterations and furthermore, may have discovered the existence of a regulatory "cross-talk" mechanism between the lower limbs whose function could be to limit leg-length-discrepancies following the breakage of growing bones.
authors.affiliation: Department of Paediatric and Adolescence Surgery, Medical University of Graz, Auenbruggerplatz 34, 8036 Graz, Austria. ee.fischerauer@gmail.com
authors.forename: Eva E
authors.initials: EE
authors.lastname: Fischerauer
authors.forename: Martin
authors.initials: M
authors.lastname: Manninger
authors.forename: Maximilian
authors.initials: M
authors.lastname: Seles
authors.forename: Gregor
authors.initials: G
authors.lastname: Janezic
authors.forename: Karin
authors.initials: K
authors.lastname: Pichler
authors.forename: Birgit
authors.initials: B
authors.lastname: Ebner
authors.forename: Annelie M
authors.initials: AM
authors.lastname: Weinberg
mesh_terms: D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000235:genetics / Q000378:metabolism; D055415:Bone Morphogenetic Protein 4 / Q000235:genetics / Q000378:metabolism; D055418:Bone Morphogenetic Protein 6 / Q000235:genetics* / Q000378:metabolism; D055419:Bone Morphogenetic Protein 7 / Q000235:genetics / Q000378:metabolism; D052005:Bone Morphogenetic Protein Receptors, Type I / Q000235:genetics* / Q000378:metabolism; D019902:Chondrocytes / Q000502:physiology; D018483:Diaphyses / Q000293:injuries / Q000502:physiology; D017102:Fracture Healing / Q000502:physiology*; D006132:Growth Plate / Q000502:physiology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D000072042:Salter-Harris Fractures; D013977:Tibia / Q000293:injuries / Q000502:physiology; D013978:Tibial Fractures / Q000235:genetics / Q000503:physiopathology*; D015854:Up-Regulation / Q000502:physiology
chemical_list: C525720:Bmp2 protein, rat; C525811:Bmp4 protein, rat; C525818:Bmp6 protein, rat; C525821:Bmp7 protein, rat; D055396:Bone Morphogenetic Protein 2; D055415:Bone Morphogenetic Protein 4; D055418:Bone Morphogenetic Protein 6; D055419:Bone Morphogenetic Protein 7; C498213:Bmpr1a protein, rat; D052005:Bone Morphogenetic Protein Receptors, Type I