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.