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Osteoblasts Suppress Bone Resorption Via Production of Osteoprotegerin

34 Pages Posted: 14 Apr 2020 Publication Status: Review Complete

See all articles by Keisha M. Cawley

Keisha M. Cawley

University of Arkansas for Medical Sciences - Center for Musculoskeletal Disease Research

Nancy Cecile Bustamante-Gomez

University of Arkansas for Medical Sciences - Center for Musculoskeletal Disease Research

Anveshi G. Guha

University of Arkansas for Medical Sciences - Center for Musculoskeletal Disease Research

Ryan S. MacLeod

University of Arkansas for Medical Sciences - Center for Musculoskeletal Disease Research

Jinhu Xiong

University of Arkansas for Medical Sciences - Center for Musculoskeletal Disease Research

Igor Gubrij

University of Arkansas for Medical Sciences - Center for Musculoskeletal Disease Research

Yu Liu

University of Arkansas for Medical Sciences - Center for Musculoskeletal Disease Research

Robin Mulkey

University of Arkansas for Medical Sciences

Michela Palmieri

University of Arkansas for Medical Sciences - Center for Musculoskeletal Disease Research

Jeff D. Thostenson

University of Arkansas for Medical Sciences - Center for Musculoskeletal Disease Research

Joseph J. Goellner

University of Arkansas for Medical Sciences - Center for Musculoskeletal Disease Research

Charles A. O'Brien

University of Arkansas for Medical Sciences - Center for Musculoskeletal Disease Research

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Abstract

Osteoprotegerin (OPG) inhibits the ability of receptor activator of NFkB ligand (RANKL) to stimulate the differentiation, activity, and survival of bone resorbing osteoclasts. Genetic studies in mice show that osteocytes are an important source of RANKL, but the cellular sources of OPG are unclear. We used conditional deletion of Tnfrsf11b, which encodes OPG, from different cell populations to identify functionally relevant sources of OPG in mice. Deletion from B lymphocytes and osteocytes, two cell types commonly thought to supply OPG, had little or no impact on bone mass. In contrast, deletion of Tnfrsf11b from osteoblasts increased bone resorption and reduced bone mass to an extent similar to germline deletion, demonstrating that osteoblasts are an essential source of OPG. These results suggest that, in addition to producing new bone matrix, osteoblasts also play an active role in terminating the resorption phase of the bone remodeling cycle by suppressing RANKL activity.

Keywords: osteoclast, osteoblast, osteocyte, OPG, RANKL, bone, remodeling

Suggested Citation

Cawley, Keisha M. and Bustamante-Gomez, Nancy Cecile and Guha, Anveshi G. and MacLeod, Ryan S. and Xiong, Jinhu and Gubrij, Igor and Liu, Yu and Mulkey, Robin and Palmieri, Michela and Thostenson, Jeff D. and Goellner, Joseph J. and O'Brien, Charles A., Osteoblasts Suppress Bone Resorption Via Production of Osteoprotegerin. Available at SSRN: https://ssrn.com/abstract=3565032 or http://dx.doi.org/10.2139/ssrn.3565032
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Keisha M. Cawley

University of Arkansas for Medical Sciences - Center for Musculoskeletal Disease Research

United States

Nancy Cecile Bustamante-Gomez

University of Arkansas for Medical Sciences - Center for Musculoskeletal Disease Research

United States

Anveshi G. Guha

University of Arkansas for Medical Sciences - Center for Musculoskeletal Disease Research

United States

Ryan S. MacLeod

University of Arkansas for Medical Sciences - Center for Musculoskeletal Disease Research

United States

Jinhu Xiong

University of Arkansas for Medical Sciences - Center for Musculoskeletal Disease Research

United States

Igor Gubrij

University of Arkansas for Medical Sciences - Center for Musculoskeletal Disease Research

United States

Yu Liu

University of Arkansas for Medical Sciences - Center for Musculoskeletal Disease Research

United States

Robin Mulkey

University of Arkansas for Medical Sciences

4301 W. Markham St.
Suite 605
Little Rock, AR 72205
United States

Michela Palmieri

University of Arkansas for Medical Sciences - Center for Musculoskeletal Disease Research

United States

Jeff D. Thostenson

University of Arkansas for Medical Sciences - Center for Musculoskeletal Disease Research

United States

Joseph J. Goellner

University of Arkansas for Medical Sciences - Center for Musculoskeletal Disease Research

United States

Charles A. O'Brien (Contact Author)

University of Arkansas for Medical Sciences - Center for Musculoskeletal Disease Research ( email )

United States

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