Differences in the Ability of Mandibular and Femur Derived Osteoclast to Support Osteoblast Activity
The skeleton is a dynamic organ that is constantly being remodeled. To maintain the integrity of the skeletal system during adulthood, the activity of osteoclasts, the bone cells responsible for bone resorption, must be balanced with the activity of osteoblasts, the bone cells responsible for bone formation. It has been understood for some time that osteoclasts secrete factors that promote osteoblast activity, thereby allowing a coupling between bone resorption and bone formation 1,2. The Mansky lab is interested in osteoclast regulation at different skeletal sites. They recently performed bulk RNA sequencing of osteoclast precursors (i.e. monocytes) from 1-year-old mice at different skeletal sites, the mandible and femur. Interestingly, mandible-derived monocytes had increased expression of osteogenic factors such as WNTs (wingless related integration site) and BMPs (bone morphogenetic proteins), suggesting that mandibular-derived osteoclasts may have an enhanced ability to promote osteoblast differentiation and activity3. To couple osteoclast and osteoblast activity, osteoblasts must proliferate and migrate to sites of bone resorption. I hypothesize that mandible-derived osteoclasts will promote the enhancement of proliferation and migration of osteoblast precursors compared to femur-derived osteoclasts. Conditioned media was collected from various stages of osteoclast differentiation. Proliferation was measured using a CCK8 assay and migration was measured using a transwell assay. Out of all the conditions tested, only mature femur-derived osteoclasts from 1 year old mice demonstrated a significant enhancement of osteoblast proliferation compared to osteoblasts treated with only osteoclast media. For migration mature femur-derived osteoclasts demonstrated a trend (p=0.08) towards enhancement of osteoblast migration. Contrary to my hypothesis, neither proliferation nor migration were enhanced with conditioned media from mandibular-derived osteoclasts. Future experiments will involve testing if mandibular- and femur-derived osteoclasts enhance osteoblast mineralization. In combination these experiments will help to understand mechanistic differences between osteoclasts from different skeletal sites.