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

## TL;DR

This study finds that osteoclasts from the jaw of older mice are larger but less active compared to those from leg bones, with distinct gene expression patterns.

## Contribution

The study reveals site-specific differences in osteoclast differentiation and gene regulation in aging, focusing on craniofacial versus long bones.

## Key findings

- Mandibular-derived osteoclasts are larger but fewer and less active than femur-derived osteoclasts in aging mice.
- Mandibular-derived monocytes show enriched WNT signaling and biomineralization genes, while femur-derived monocytes are enriched for mitochondrial respiratory complex I genes.

## Abstract

Osteoclasts are the cells that resorb bone and increase their activity as men and women age. This study investigates if osteoclasts from different skeletal sites change via similar mechanisms during aging. We determined that osteoclasts from the bones of the face of older mice are larger in size but have decreased activity compared to osteoclasts from leg bones. Transcriptomic analysis revealed that different pathways are up or downregulated in facial-derived osteoclasts compared to leg-derived osteoclasts. This information is important so that we can begin to understand if there are skeletal site-specific changes that occur in osteoclasts during the aging process. Lastly, this information may eventually lead to a better understanding of the mechanisms that regulate skeletal conditions such as osteoporosis or periodontal disease, which occur more frequently as a person ages.

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.