Title: Effect of Voluntary Wheel-Running Exercise on Osteocytes in Aged Mice
Kaitlyn Tom (Presenter)
University of Missouri-Kansas City
LeAnn Tiede-Lewis, University of Missouri-Kansas City
Mark Dallas, University of Missouri-Kansas City
Yixia Xie, University of Missouri-Kansas City
Sarah Dallas, University of Missouri-Kansas City
Objectives: Aging is associated with loss of bone mass and increased fracture risk. Recent discoveries that osteocytes play key roles in regulating bone mass have highlighted the osteocyte as a target for developing therapies to prevent bone loss. Using a mouse model of aging, we previously showed that aging is associated with loss of osteocyte dendricity, followed by a decline in osteocyte number. The goal of this study was to determine whether voluntary wheel running exercise could slow the age-related decline in osteocyte dendrite connectivity and correlate changes in osteocyte connectivity with alterations in bone mass and structure.
Methods: 12 month female C57BL/6 mice (n=8) underwent 6 months of voluntary wheel running (VWR), with daily activity recorded. Femurs were harvested at 18mo. Control mice (n=8) were singly housed without wheel access. Another group of VWR and control mice (n=4) were sacrificed at 22mo (i.e. 10 mo of VWR). Decalcified sections of the left femur were stained with phalloidin & DAPI for confocal imaging and 3D analysis of osteocyte number and connectivity. The right femur was used for microCT analysis of cortical & trabecular bone, followed by histology and bone histomorphometry.
Results: Wheel running mice ran an average of 3.4 km/day over the 6mo VWR period and 3.9 km/day over 10 mo. Maximal running activity occurred in the first 8-10wks of VWR, which plateaued to ~2.5km/day for the remainder of the exercise period. 6mo of VWR was associated with increased osteocyte dendrite number, but no significant change in osteocyte number/mm3. This increase was not maintained after 10mo of VWR. Cortical BV/TV, perimeter, thickness, bone area closed porosity, and trabecular BV/TV were not significantly different in VWR mice vs. control. A dramatic increase in marrow adipose cells was seen in 22mo mice, which was completely prevented by 10mo of VWR.
These results suggest that initiating exercise at 12mo can slow dendrite loss and improve osteocyte connectivity in aged female mice up to 18 mo of age but that the effect was not maintained out to 22mo. However, exercise had a dramatic effect to reduce marrow fat with advanced age. Exercise therefore may both retain osteocyte function and reduce marrow fat to maintain bone health with aging. Supported by UMKC SOD Summer Scholars Program.