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.

Public Health Relevance

Radiotherapy is a standard of care for head and neck cancers. It is often complicated by jaw osteoradionecrosis because bone cells needed for tissue regeneration become damaged by radiation. We will use stem cells and animal systems to understand mechanisms promoting jaw necrosis and how to prevent them. The goal is to improve quality of life of cancer survivors.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Career Transition Award (K22)
Project #
5K22CA169089-02
Application #
8546712
Study Section
Subcommittee G - Education (NCI)
Program Officer
Wali, Anil
Project Start
2012-09-17
Project End
2015-08-31
Budget Start
2013-09-01
Budget End
2014-08-31
Support Year
2
Fiscal Year
2013
Total Cost
$196,344
Indirect Cost
$14,544
Name
University of Pennsylvania
Department
Dentistry
Type
Schools of Dentistry
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Akintoye, Sunday O; Greenberg, Martin S (2014) Recurrent aphthous stomatitis. Dent Clin North Am 58:281-97
Akintoye, So (2014) Osteonecrosis of the jaw from bone anti-resorptives: impact of skeletal site-dependent mesenchymal stem cells. Oral Dis 20:221-2
Chandra, Abhishek; Lin, Tiao; Tribble, Mary Beth et al. (2014) PTH1-34 alleviates radiotherapy-induced local bone loss by improving osteoblast and osteocyte survival. Bone 67:33-40
Turner, Lena; Mupparapu, Muralidhar; Akintoye, Sunday O (2013) Review of the complications associated with treatment of oropharyngeal cancer: a guide for the dental practitioner. Quintessence Int 44:267-79
Akintoye, Sunday O; Boyce, Alison M; Collins, Michael T (2013) Dental perspectives in fibrous dysplasia and McCune-Albright syndrome. Oral Surg Oral Med Oral Pathol Oral Radiol 116:e149-55