title: B Cell Production of Both OPG and RANKL is Significantly Increased in Aged Mice.
abstract: Aging is a risk factor for osteoclastic bone loss and bone fracture. Receptor activator of NF-κB 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.
authors.affiliation: Division of Endocrinology and Metabolism and Lipids, Department of Medicine, Emory University School of Medicine, Atlanta, GA, 30322, USA ; Emory Winship Cancer Institute, Emory University, Atlanta, GA, 30322, USA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Division of Endocrinology and Metabolism and Lipids, Department of Medicine, Emory University School of Medicine, Atlanta, GA, 30322, USA.
authors.forename: Masakazu
authors.initials: M
authors.lastname: Terauchi
authors.affiliation: Division of Endocrinology and Metabolism and Lipids, Department of Medicine, Emory University School of Medicine, Atlanta, GA, 30322, USA.
authors.forename: Tatyana
authors.initials: T
authors.lastname: Vikulina
authors.affiliation: Atlanta Department of Veterans Affairs Medical Center, Decatur, Georgia 30033, USA.
authors.forename: Susanne
authors.initials: S
authors.lastname: Roser-Page
authors.affiliation: Division of Endocrinology and Metabolism and Lipids, Department of Medicine, Emory University School of Medicine, Atlanta, GA, 30322, USA ; Emory Winship Cancer Institute, Emory University, Atlanta, GA, 30322, USA ; Atlanta Department of Veterans Affairs Medical Center, Decatur, Georgia 30033, USA.
authors.forename: M N
authors.initials: MN
authors.lastname: Weitzmann
keywords: Aging; B cells; OPG; Osteoclast; Osteoporosis; RANKL