Kim Mansky, PhD
Characterization of Mandibular Osteoclast Progenitors during Physiological and Bone Healing
Dr. Kim Mansky is a professor at the University of Minnesota School of Dentistry. Since coming to the University of Minnesota as an assistant professor Dr. Mansky’s research has focused on epigenetic regulators of osteoclast gene expression. She obtained her PhD from the University of Wisconsin-Madison studying papilloma viruses. After her PhD studies, she completed a postdoctoral fellowship at The Ohio State University researching regulation of osteoclast gene expression. She has published over 45 journal articles and serves on NIH study section for NIDCR as well as the editorial board of JBMR Plus. Besides her emphasis on research Dr. Mansky recently received funding for a summer research program to encourage underrepresented populations in STEM to consider careers in oral and craniofacial biology.
Osteoclasts are multinuclear bone resorbing cells derived from myeloid lineage. Osteoclast activity within craniofacial bones facilitates critical developmental processes such as tooth eruption and skull modeling. Recent lineage tracing experiments in mice demonstrate that craniofacial activity by osteoclasts requires embryonic, but not adult myeloid cells. These data suggest fundamental differences between adult bone marrow- as compared to embryonic-derived tissue resident osteoclast cell populations; however, we lack essential knowledge about the osteoclast progenitors found in the marrow of craniofacial bones. While recent studies suggest unique molecular signatures of mineral resorbing cells within different skeletal sites, the bulk of our knowledge and understanding of osteoclast progenitors is derived from long bones. Moreover, we completely lack transcriptomic data describing craniofacial-derived osteoclast progenitors. Osteoclasts differentiated from bone marrow of the mandible are significantly larger and have increased expression of osteoclast genes compared to femur-derived osteoclasts. In the first aim we will perform scRNA-seq from mandible and femur derived bone marrow to identify critical gene/pathway signatures, unique to the two skeletal sites. Using flow cytometry, we will determine if the composition of cells is different in the two skeletal sites. In the second aim we will perform conditioned media experiments with mandible and femur derived CX3CR1+ cells to determine if there are differences in their osteogenic ability. Using our scRNA-seq data, we will identify factors responsible for the enhancement of bone regeneration by osteoclasts. We will also use lineage tracing experiments to determine which precursor cell populations are recruited to a mandibular injury. In total these experiments will allow us to identify critical differences between the mandible- and femur-derived osteoclasts that will impact bone regeneration.