Aging decreases osteocyte lacunar-canalicular turnover in female C57BL/6 mice

Abstract

Osteocytes engage in bone resorption and mineralization surrounding their expansive lacunar-canalicular system (LCS) through LCS turnover. However, fundamental questions persist about where, when, and how often osteocytes engage in LCS turnover and how these processes change with aging. Furthermore, whether LCS turnover depends on tissue strain remains unexplored. To address these questions, we utilized confocal scanning microscopy, immunohistochemistry, and scanning electron microscopy to characterize osteocyte LCS turnover in the cortical (mid-diaphysis) and cancellous (metaphysis) femurs from young (5 mo) and early-old-age (22 mo) female C57BL/6JN mice. LCS bone mineralization was measured by the presence of perilacunar fluorochrome labels. LCS bone resorption was measured by immunohistochemical markers of bone resorption. The dynamics of LCS turnover were estimated from serial fluorochrome labeling, where each mouse was administered two labels between 2 days and 16 days before euthanasia. Osteocyte participation in mineralizing their surroundings is highly abundant in both cortical and cancellous bone of young adult mice but significantly decreases with aging. LCS bone resorption also decreases with aging. Aging has a greater impact on LCS turnover dynamics in cancellous bone than in cortical bone. Lacunae with recent LCS turnover have larger lacunae in both age groups. The impacts of aging on LCS turnover also varies with cortical region of interest and intracortical location, suggesting a dependence on tissue strain. The impact of aging on decreasing LCS turnover may have significant implications for bone quality and mechanosensation. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=88 SRC="FIGDIR/small/571934v1_ufig1.gif" ALT="Figure 1"> View larger version (49K): org.highwire.dtl.DTLVardef@cbb7a9org.highwire.dtl.DTLVardef@86d667org.highwire.dtl.DTLVardef@660eb8org.highwire.dtl.DTLVardef@5062a6_HPS_FORMAT_FIGEXP M_FIG Graphical abstractOsteocyte participation in lacunar-canalicular system (LCS) mineralization is abundant in young mice but decreases with aging in both cortical and cancellous bone. Aging also reduces LCS bone resorption. Aging alters the relationship between LCS turnover and variation in cortical tissue strain. C_FIG