BMP‐6 and BMPR‐1a are up‐regulated in the growth plate of the fractured tibia

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. © 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 31: 357–363, 2013