Aging impairs the osteocytic regulation of collagen integrity and bone quality

Charles A. Schurman, Serra Kaya, Neha Dole, Nadja M.Maldonado Luna, Natalia Castillo, Ryan Potter, Jacob P. Rose, Joanna Bons, Christina D. King, Jordan B. Burton, Birgit Schilling, Simon Melov, Simon Tang, Eric Schaible, Tamara Alliston

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Poor bone quality is a major factor in skeletal fragility in elderly individuals. The molecular mechanisms that establish and maintain bone quality, independent of bone mass, are unknown but are thought to be primarily determined by osteocytes. We hypothesize that the age-related decline in bone quality results from the suppression of osteocyte perilacunar/canalicular remodeling (PLR), which maintains bone material properties. We examined bones from young and aged mice with osteocyte-intrinsic repression of TGFβ signaling (TβRIIocy−/−) that suppresses PLR. The control aged bone displayed decreased TGFβ signaling and PLR, but aging did not worsen the existing PLR suppression in male TβRIIocy−/− bone. This relationship impacted the behavior of collagen material at the nanoscale and tissue scale in macromechanical tests. The effects of age on bone mass, density, and mineral material behavior were independent of osteocytic TGFβ. We determined that the decline in bone quality with age arises from the loss of osteocyte function and the loss of TGFβ-dependent maintenance of collagen integrity.

Original languageEnglish
Article number13
JournalBone Research
Volume12
Issue number1
DOIs
StatePublished - Dec 2024

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