Complications of Jaw Osteoradionecrosis in Cancer Management

描述（由申请人提供）：骨放射性坏死（ORN）是癌症治疗的主要并发症，可导致面部毁容，牙齿脱落，显著发病率，虚弱和生活质量下降。颌骨易患ORN的因素尚不清楚。我们之前的研究表明，人骨间充质干细胞的成骨和骨再生特性取决于胚胎起源部位，我们将阐明辐射诱导的潜在细胞事件，这些细胞事件调节了辐射后颌骨愈合的失调。我们假设辐射不同程度地调节颌骨破骨细胞-成骨细胞平衡以促进坏死。我们将确定不同辐射引起的缺氧如何加速颌骨ORN。了解骨间充质干细胞对辐射的反应性，对于提高癌症幸存者生活质量的预防性治疗的发展至关重要。

DESCRIPTION (provided by applicant): Osteoradionecrosis (ORN) is major complication of cancer therapy that causes facial disfigurement, tooth loss, significant morbidity, debility and diminished quality of life. Factors that make the jaw highly susceptible to ORN are still unclear. Guided by our previous work demonstrating that osteogenesis and bone regenerative properties of human bone mesenchymal stem cells are skeletal site-dependent according to embryological site of origin, we will elucidate underlying radiation-induced cellular events that dysregulate jaw bone healing after irradiation. We hypothesize that radiation disparately regulate jaw osteoclast-osteoblast balance to promote necrosis. We will determine how differential radiation-induced hypoxia accelerates jaw ORN. Understanding the responsiveness of bone mesenchymal stem cells to irradiation is critical to development of preventive therapies that will improve quality o life of cancer survivors.