Local Production of Osteoprotegerin by Osteoblasts Suppresses Bone Resorption.

Autor:	Cawley KM; Center for Musculoskeletal Disease Research, University of Arkansas for Medical Sciences, Little Rock, AR, USA; Division of Endocrinology, University of Arkansas for Medical Sciences, Little Rock, AR, USA., Bustamante-Gomez NC; Center for Musculoskeletal Disease Research, University of Arkansas for Medical Sciences, Little Rock, AR, USA; Division of Endocrinology, University of Arkansas for Medical Sciences, Little Rock, AR, USA., Guha AG; Center for Musculoskeletal Disease Research, University of Arkansas for Medical Sciences, Little Rock, AR, USA; Division of Endocrinology, University of Arkansas for Medical Sciences, Little Rock, AR, USA., MacLeod RS; Center for Musculoskeletal Disease Research, University of Arkansas for Medical Sciences, Little Rock, AR, USA; Division of Endocrinology, University of Arkansas for Medical Sciences, Little Rock, AR, USA., Xiong J; Center for Musculoskeletal Disease Research, University of Arkansas for Medical Sciences, Little Rock, AR, USA; Department of Orthopaedic Surgery, University of Arkansas for Medical Sciences, Little Rock, AR, USA., Gubrij I; Center for Musculoskeletal Disease Research, University of Arkansas for Medical Sciences, Little Rock, AR, USA; Division of Endocrinology, University of Arkansas for Medical Sciences, Little Rock, AR, USA., Liu Y; Center for Musculoskeletal Disease Research, University of Arkansas for Medical Sciences, Little Rock, AR, USA; Division of Endocrinology, University of Arkansas for Medical Sciences, Little Rock, AR, USA., Mulkey R; Division of Laboratory Animal Medicine, University of Arkansas for Medical Sciences, Little Rock, AR, USA., Palmieri M; Center for Musculoskeletal Disease Research, University of Arkansas for Medical Sciences, Little Rock, AR, USA; Division of Endocrinology, University of Arkansas for Medical Sciences, Little Rock, AR, USA., Thostenson JD; Center for Musculoskeletal Disease Research, University of Arkansas for Medical Sciences, Little Rock, AR, USA; Department of Biostatistics, University of Arkansas for Medical Sciences, Little Rock, AR, USA., Goellner JJ; Center for Musculoskeletal Disease Research, University of Arkansas for Medical Sciences, Little Rock, AR, USA; Division of Endocrinology, University of Arkansas for Medical Sciences, Little Rock, AR, USA., O'Brien CA; Center for Musculoskeletal Disease Research, University of Arkansas for Medical Sciences, Little Rock, AR, USA; Division of Endocrinology, University of Arkansas for Medical Sciences, Little Rock, AR, USA; Department of Orthopaedic Surgery, University of Arkansas for Medical Sciences, Little Rock, AR, USA; Central Arkansas Veterans Healthcare System, Little Rock, AR, USA. Electronic address: caobrien@uams.edu.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2020 Sep 08; Vol. 32 (10), pp. 108052.
DOI:	10.1016/j.celrep.2020.108052
Abstrakt:	Osteoprotegerin (OPG) inhibits the ability of receptor activator of nuclear factor κB (NF-κB) 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 use 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, has little or no impact on bone mass. By contrast, deletion of Tnfrsf11b from osteoblasts increases bone resorption and reduces 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. Competing Interests: Declaration of Interests C.A.O. owns stock in Radius Health. The remaining authors declare no competing interests. (Published by Elsevier Inc.)
Databáze:	MEDLINE
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