TY - JOUR
T1 - Aging impairs the osteocytic regulation of collagen integrity and bone quality
AU - Schurman, Charles A.
AU - Kaya, Serra
AU - Dole, Neha
AU - Luna, Nadja M.Maldonado
AU - Castillo, Natalia
AU - Potter, Ryan
AU - Rose, Jacob P.
AU - Bons, Joanna
AU - King, Christina D.
AU - Burton, Jordan B.
AU - Schilling, Birgit
AU - Melov, Simon
AU - Tang, Simon
AU - Schaible, Eric
AU - Alliston, Tamara
N1 - Publisher Copyright:
© The Author(s) 2024.
PY - 2024/12
Y1 - 2024/12
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85185944646&partnerID=8YFLogxK
U2 - 10.1038/s41413-023-00303-7
DO - 10.1038/s41413-023-00303-7
M3 - Article
C2 - 38409111
AN - SCOPUS:85185944646
SN - 2095-4700
VL - 12
JO - Bone Research
JF - Bone Research
IS - 1
M1 - 13
ER -