Physeal Reactions To Growth Plate Lesions - Focusing On Specific Physeal Molecular Pathways (BMP-2)

Abstract

The inhibiting growth disturbance is associated with a partial or complete growth arrest due to the formation of physeal bone-bridges. The aim of this study is to elucidate BMP-2 expression in the process of physeal repair mechanisms in a physeal injury animal model. BMP-2 is a key signalling growth factor in the process of endochondral ossification at the growth plate. We hypothesise that deregulated BMP expression is involved in bone bridge formation after physeal injury. Experimental Sprague-Dawley rats were subjected to a unilateral transepiphyseal drill-hole injury of the left proximal tibial growth plate. After euthanasia on days 1, 3, 7, 14, 28, and 82 post-injury, growth plate tissue of the left and right tibiae of the experimental and control animals were harvested and prepared for immunohistochemistry according to standardized protocols. The temporal-spatial expression of BMP-2 at the drill-hole injured growth plate suggests potential roles in the inflammatory response, as well as in the fibrogenic, osteogenic responses and in bone remodelling at the injured growth plate. On day 1 the resting zone and resorption zone were weakly positive. On day 3 BMP-2 positive immunostaining was observed in the RZ and proliferating zone. At day 7 mesenchymal cells, osteoblasts were highly stained positive, whereas the PZ showed highest staining. At day 14 a less positive immunostaining was observed compared to the growth plate and mesenchymal cells on day 1, 3 and 7. Cells of the growth plate next to the injury and mesenchymal cells along the drill-hole injury showed a denser positive staining compared to cells lateral of the defect. Day 28, 42 and 82 nearly the whole growth plate showed an abundant immunostaining, whereas cells of the PZ showed the highest. These findings demonstrate a BMP-2 signalling gradient across the epiphyseal plate. This study provides evidence that the healing process after a transepiphyseal injury involves the whole growth plate by stimulating chondrocyte proliferation and differentiation in growth plate cartilage by the expression of BMP-2. In addition, the results show that besides the early inflammatory phase, BMP-2 may also play an important role in bone formation/maturation and in bone bridge remodeling in the injured growth plate. The spatial differential expression of BMP-2 in the injured leg suggests that BMP-2 has a critical and potential role in regulating the cellular events leading to the formation of bone bridges.

Datum der Bewilligung	2011
Originalsprache	Englisch
Gradverleihende Hochschule	Medizinische Universität Graz
Betreuer/-in	Annelie-Martina Weinberg (Betreuer*in)