Mandibular-Derived Monocytes from 1-Year-Old Mice Have Enhanced Osteoclast Differentiation and Differentially Regulated Gene Expression Compared to Femur-Derived Monocytes

Abstract

It is well established that both men and women lose bone as they age. While recent studies suggest unique molecular signatures of mineral-resorbing cells at different anatomical locations, most studies focus on long bones, and little is known about craniofacial osteoclasts, especially during the aging process. To determine differences between osteoclasts at different skeletal sites, we analyzed the differentiation potential, demineralization activity, and gene expression of osteoclast precursors from 1-year-old male and female C57Bl/6J mice. In our study, we determined that mandibular-derived osteoclasts were larger in size compared to those in the femur but were significantly fewer in number. However, femur-derived osteoclasts demineralized larger and more numerous areas of a calcium phosphate surface compared to mandibular-derived osteoclasts. Bulk RNA sequencing demonstrated that the mandibular-derived monocytes were enriched for genes in the WNT signaling pathway, biomineralization, and osteogenesis pathways, while femur-derived monocytes were enriched for genes in the mitochondrial respiratory complex I. Overall, our data suggest that there are different mechanisms that regulate osteoclasts from different skeletal sites as we age. This information may help to guide the design of treatments to prevent aging-induced bone loss.

Keywords

• monocytes
• osteoclasts
• osteogenesis
• electron transport
• respiratory chain