Abstract 44

ACTIVATION OF MAP KINASE p38 AND UP-REGULATION OF CYTOKINES TNF-a AND IL-1-ß AT INJURED GROWTH PLATE

FH-H Zhou, BK Foster, XF Zhou*, and CJ Xian

Department of Orthopaedic Surgery, University of Adelaide Department of Paediatrics, Women's and Children's Hospital, North Adelaide 5006; and *Flinders University Department of Human Physiology, GPO Box 2100, Adelaide 5001.

The growth plate cartilage is a fragile area of the growing long bone and has a limited ability to regenerate after fracture. Previously, we have characterised the injury responses and cellular mechanisms for the bony repair of the injured growth plate however, the underlying molecular mechanisms remain unknown. Activated p38 mitogen-activated protein kinase (MAPK) interacts with proinflammatory cytokines to transduce injury induced stress signals and regulate cell functions. In this study, we examined activation of p38 and expression of TNF-a and IL-1-ß at the injured proximal tibial growth plate of young rats by Western blot analysis, real-time RT-PCR and immunohistochemistry. Results showed 4-6 folds increase in phosphorylation of p38 from 8 to 24 hours post injury and levels declined by day 3. Immunolocalisation of activated p38 showed nuclear and cytoplasmic staining in neutrophils and macrophages at the injury site, and in chondrocytes at the adjacent growth plate. The activation of p38 during this inflammatory phase coincided with up-regulated expression of TNF-a and IL-1ß mRNA 24 and 8 hours post injury, respectively. In addition, both TNF-a and IL-1ß were immunolocalised in the inflammatory cells at the injury site. Our results suggest that activation of p38 may be associated with up-regulation of IL-1ß and TNF-a during the inflammatory response at the injured growth plate. Due to their known functions in affecting cell migration and bone cell differentiation, their up-regulation may play a role in regulating subsequent responses for the bony repair of injured growth plate.

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