Researchers at UTHealth Houston have been awarded an $8.1 million grant by the National Institutes of Health (NIH) to examine skeletal stem cells as potential drivers of craniofacial bone diseases and deformities. The study is led by Noriaki Ono, DDS, PhD, associate professor of orthodontics, and diagnostic and biomedical sciences at UTHealth Houston School of Dentistry.
Bones in the craniofacial region are highly susceptible to diseases because of the demands of chewing, breathing, and swallowing, which can impact bone growth and regeneration. In previous research, Ono identified a type of skeletal stem cell inside the growth plate and bone marrow in mice. While the cartilaginous tissue forming into bone is an essential part of bone growth in fetal development, it is often overlooked because it is in a "resting zone" where the stem cells stay inactive until they are needed. Ono and his team tracked the stem cells to follow the life cycle and discovered some cells, previously believed inactive, were actually continuing to make bone.
We are now trying to understand the mechanisms of these craniofacial bone diseases through the lens of bone-forming skeletal stem cells. We want to understand how these stem cells are contributing to bone diseases in the oral and craniofacial region so that in the future, we can come up with better therapeutic modalities to cure these conditions."
Noriaki Ono, DDS, PhD, associate professor of orthodontics, and diagnostic and biomedical sciences at UTHealth Houston School of Dentistry
The National Institute of Dental and Craniofacial Research grant will fund the study over eight years. The study will be implemented in three programs using genetically engineered mice. The first program will investigate how periosteal and endosteal stem cells function together in craniofacial bones and contribute to bone formation. The different contributions of periosteum and endosteum to bone repair suggest differences in the stem cell populations and tissue environments; understanding these differences could help treat bone diseases and fractures.
"What makes the skull bone unique is that there is a mixture of two different mechanisms of bone formation involved, so in this phase, we will look at the stem cells in the intramembranous pathway so that we can better understand the behavior and function of these types of cells," Ono said.
The second program will focus on how chondrocytes, cartilage-making cells, develop into craniofacial bones. Researchers will compare the normal stem cell to a genetically modified cell to define the mechanisms regulating healthy maturing in the craniofacial cartilage, giving researchers an idea of how changes in regular gene activity may contribute to disease.
The third program will help researchers further discern the role of skeletal stem cells in craniofacial bone diseases by analyzing two conditions: idiopathic condylar resorption, the breakdown and loss of bone in the jaw joint condyle, and osteonecrosis of the jaw, a condition where bone cells die due to various causes.
"We are going to be able to track the fate of these stem cells over time. By doing this research, we will know that when bone-making stem cells misbehave, many problems happen in the skull and face bones, such as bone deformities," Ono said. "This means that we may be able to treat bone diseases in the jaw and skull that we often see in dental clinics or other clinical settings by specifically treating bone-making stem cells."
Ono's research focuses on the fundamental biology of skeletal stem cells, with a further scope of understanding the pathophysiology of dental, craniofacial, and skeletal deformities and other diseases that affect millions of children and adults. The NIH has supported his research since 2012.
Joshua Welch, PhD, with the University of Michigan, was a co-investigator on the study. The grant number for the award from the National Institute of Dental and Craniofacial Research, part of the NIH, is R35DE034348.
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