Mouse mandibular–derived osteoclast progenitors have differences in intrinsic properties compared with femoral–derived progenitors

Abstract

Abstract Craniofacial osteoclasts are essential for site–specific processes such as alveolar bone resorption, tooth eruption, and orthodontic tooth movement. Much of the current understanding of osteoclast development and function comes from studies using long bone–derived cells. Minimal investigation has been done to explore skeletal site differences. The overall goal of this study was to determine if mandibular– and femoral–derived osteoclasts represent distinct populations. To test this hypothesis, bone marrow cells were initially analyzed from the mandible and femur of 2–month–old mice. It was shown that mandibular–derived osteoclasts have enhanced size (mm2) compared with femoral–derived osteoclasts. Since bone marrow macrophages are a heterogenous population, we additionally selected for monocytes and demonstrated that mandibular–derived monocytes also form osteoclasts with increased size compared with femoral–derived monocytes. Osteoclast precursor populations from both skeletal sites were analyzed by flow cytometry. A newly described Ly6CHigh+ population as well as the Ly6Cint population was increased in the mandibular–derived cells. The difference in differentiation potential between monocyte cultures suggests that the increase in the Ly6CHigh+ population may explain the enhanced differentiation potential in mandibular–derived cells. Monocyte genes such as Pu.1, C/ebp-a, and Prdm1 are increased in expression in mandibular–derived monocytes compared with femoral–derived monocytes. As expected with enhanced differentiation, osteoclast genes including Nfatc1, Dc-stamp, Ctsk, and Rank are upregulated in mandibular–derived osteoclast precursors. Future studies will determine how changes in the environment of the mandible lead to changes in percentages of osteoclast progenitors and their differentiation potential.