2017
DOI: 10.18632/aging.101308 View full text |Buy / Rent full text
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Abstract: Age-related bone loss and associated fracture risk are major problems in musculoskeletal health. Osteocytes have emerged as key regulators of bone mass and as a therapeutic target for preventing bone loss. As aging is associated with changes in the osteocyte lacunocanalicular system, we focused on the responsible cellular mechanisms in osteocytes. Bone phenotypic analysis was performed in young-(5mo) and aged-(22mo) C57BL/6 mice and changes in bone structure/geometry correlated with alterations in osteocyte pa… Show more

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“…Numerous studies have demonstrated the critical role that osteocytes play in sensing mechanical stimuli and coordinating targeted bone remodeling to repair damaged areas . Decreases in osteocyte viability have been observed in many conditions underlying bone loss . However, the specific mechanisms by which viable osteocytes prevent bone fragility in aging are not known.…”
Section: Discussionmentioning
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“…Numerous studies have demonstrated the critical role that osteocytes play in sensing mechanical stimuli and coordinating targeted bone remodeling to repair damaged areas . Decreases in osteocyte viability have been observed in many conditions underlying bone loss . However, the specific mechanisms by which viable osteocytes prevent bone fragility in aging are not known.…”
Section: Discussionmentioning
“…Numerous studies suggest that the extensive osteocyte network within the mineralized bone matrix plays an essential role in orchestrating bone remodeling through cell‐cell communication among neighboring osteocytes and with cells on the bone surface . Consistent with this notion, old age and conditions of increased skeletal fragility are associated with reductions in osteocyte viability and increased prevalence of empty lacunae, and disruptions in the osteocyte network alter osteocytic regulation of bone remodeling . Osteocytes control intercellular signaling with distant cells both through the extracellular release of molecules and cytokines via hemichannels formed via connexins (Cx) and directly with adjacent cells through gap junction channels, formed by connexons present on the surface of neighboring cells .…”
Section: Introductionmentioning
“…Finally, there are intrinsic limitations to the animal model itself. The lifestyle associated with standard animal housing is sedentary: It was shown that old mice and rats with access to voluntary wheel running will use the option and show no age‐associated loss in osteocytes and overall better bones . In this regard, our findings are for sedentary elderly and may not be valid in a more physically active model.…”
Section: Discussionmentioning
“…Taken together, these findings suggest that defective autophagy in osteoblast lineage cells prevents the proper transition of osteoblasts into osteocytes and causes degeneration of the osteocyte canalicular network . Interestingly, the latter phenomenon has recently been associated with natural chronological aging in mice . Given that impaired autophagy in osteoblast lineage cells and osteocytes appears to be a consequence of overwhelming stress that becomes intensified in bone over time, defective autophagy may have a causal role in skeletal aging.…”
Section: Loss Of Proteostasismentioning
“…(60) Interestingly, the latter phenomenon has recently been associated with natural chronological aging in mice. (61) Given that impaired autophagy in osteoblast lineage cells and osteocytes appears to be a consequence of overwhelming stress that becomes intensified in bone over time, defective autophagy may have a causal role in skeletal aging. However, direct evidence is lacking at this time.…”
Section: Loss Of Proteostasismentioning