Cathepsin K-lineage cells and mechanical loading independently modulate bone mass in the murine tibia

The ability of bone to adapt to external mechanical loads has been extensively studied, with mechanical stimuli increasing cortical and cancellous bone mass. However, the stem cell basis underlying this response is not well understood. To date, most studies focused on the role of differentiated cell populations in the skeletal response to loading. A recently discovered periosteal-specific skeletal stem cell marked by cathepsin K (CTSK) that drives intramembranous bone formation is a promising candidate to mediate load-induced bone formation. In this study, we sought to determine the influence of CTSK-lineage cells on the skeletal response to mechanical loading. We ablated cells expressing CTSK prior to initiating cyclic tibial compression for two weeks beginning at 16 weeks of age. We analyzed cortical and cancellous bone morphology at the tibial metaphysis and cortical bone morphology at the mid-diaphysis. Loading increased cortical, but not cancellous, bone mass. The amount of bone formed in response to loading did not differ when CTSK-expressing cells were ablated. CTSK-lineage cell ablation increased cortical bone mass primarily in regions subjected to tension and loading predominantly affected regions of bone under compression. To analyze the material composition of load-induced bone, we performed Raman spectroscopy along the periosteal surface of the diaphysis. CTSK-lineage cell ablation altered the influence of loading on B-type carbonate substation, a measure of tissue age. Overall, the amount of bone formed in response to loading did not differ in the absence of CTSK-lineage cells, but the material composition of load-induced cortical tissue was altered.