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Author Notes:

Email Address: mweitzm@emory.edu

The contents of this manuscript do not represent the views of the Department of Veterans Affairs, the National Institutes of Health or the United States Government.

The authors confirm that this article content has no conflict of interest.

Subjects:

Research Funding:

MNW is supported, in part, by a grant from the Biomedical Laboratory Research & Development Service of the VA Office of Research and Development (5I01BX0-00105) and by NIAMS grants (AR053607, AR056090 and AR059364) and NIA grant AG040013.

Keywords:

  • Aging
  • B cells
  • OPG
  • Osteoclast
  • Osteoporosis
  • RANKL

B cell production of both opg and rankl is significantly increased in aged mice

Tools:

Journal Title:

Open Bone Journal

Volume:

Volume 6, Number 1

Publisher:

, Pages 8-17

Type of Work:

Article | Final Publisher PDF

Abstract:

Aging is a risk factor for osteoclastic bone loss and bone fracture. Receptor activator of NF-kB ligand (RANKL) is the key effector cytokine for osteoclastogenesis and bone resorption, and is moderated by its decoy receptor osteoprotegerin (OPG). The development of an inflammatory environment during aging leads to increased bone resorption and loss of bone mineral density (BMD). Interestingly, animal and clinical studies show that OPG is actually increased in aging but fails to fully compensate for endogenous RANKL. Osteoblast- and B-lineage cells are significant sources of physiological OPG, however osteoblast OPG production declines with age, suggesting that elevated OPG in aging may be a consequence of changes in B cell function. In this study we examined BMD and indices of trabecular bone structure during aging, and B cell production of both RANKL and OPG in young and aged mice. Our data reveal significant loss of BMD and trabecular structure with age commensurate with significantly elevated concentrations of both OPG and RANKL in aged mice, and a decline in B cell populations in aged animals. Taken together our data suggest that B cells may be responsible for the elevated concentrations of OPG during aging and are essential to counteract excessive age-associated bone resorption. Paradoxically, B cells themselves likely contribute RANKL in aging and the loss of B cells with age may further contribute to the imbalance in OPG relative to RANKL that predisposes age-associated bone loss.

Copyright information:

© Li et al.

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