NESPS - Northeastern Society of Plastic Surgeons NESPS - Northeastern Society of Plastic Surgeons
 
Members Only
Username
Password
Forgot Password?
2008 Annual Meeting Abstracts


EARLY RESPONSE OF GENE EXPRESSION IN FRACTURED MANDIBLE
Peter J. Taub, M.D., Younghui Li, PhD, Daniel Leong, MS, Leslie Cohen, BA, David T. Fung, PhD, Melissa Ramcharan, MS, Robert J. Majeska, PhD, Hui B. Sun, PhD.
Mount Sinai Medical Center, New York, NY, USA.

BACKGROUND: Bone healing, whether following traumatic injury or iatrogenic reconstruction, is a complex endeavor with no guarantee of success. Understanding the cellular and molecular mechanisms of fracture response is essential both for treating failures of bone healing and for developing effective new approaches to skeletal reconstruction. In this study we sought to elucidate critical local regulatory mechanisms of mandibular healing.
METHODS: Specifically, we investigated expression profiles of selected functional groups of genes at an early stage following mandible fracture in female Sprague-Dawley rats. Three hours after unilateral fracture of the mandibular ramus, the bone ends were harvested and mRNA expression was analyzed using reverse transcription and real-time PCR.
RESULTS: Among 31 genes analyzed, 25 genes were upregulated relative to sham-operated controls (Fig 1), including: 1) Matrix metalloproteinases (MMPs)2, 3, 9, 13 and 23; 2) pro-inflammatory cytokines and mediators IL-1β, TNFα, IL-6, IL-13, MCP-1, and NFκB; 3) homeostasis-related cytokine and signaling molecules TGFβ1, TGFβ2, TGFβ3, BMP-7, and Smad3; 4) bone remodeling-related signaling molecules MCSF, RANKL, and OPG; 5) cell-matrix adhesion molecules integrin α1 and integrin β1; 6) apoptotic and anti-apoptotic molecules BCl-2 and Bad; 7) VEGF and Hypoxia-inducible factor (HIF)-1-α. Notably, CBP/p300-interacting transactivator with ED-rich tail 2 (CITED2), a mechanosensitive regulator of MMPs that may also play a role in suppressing HIF-1-α mediated transcription, was downregulated in the fractured mandible.
CONCLUSIONS: This complex expression pattern reflects the known diversity of genes whose expression is rapidly altered in response to fracture, but also illustrates changes in some genes such as CITED2, not previously associated with fracture healing.