The RANKL/RANK/OPG pathway

Boyce, Brendan F.; Xing, Lianping

doi:10.1007/s11914-007-0024-y

Cited by 339Bone Metabolism and DiseasesBone health and osteoporosis researchOsteomyelitis and Bone Disorders Research

The RANKL/RANK/OPG pathway

Boyce, Brendan F., Xing, Lianping·2007·Current Osteoporosis Reports

DOI 10.1007/s11914-007-0024-y

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Abstract

Understanding of osteoclast formation and activation has advanced considerably since the discovery of the RANKL/RANK/OPG system in the mid 1990s. Osteoblasts and stromal stem cells express receptor activator of NF-jB ligand (RANKL), which binds to its receptor, RANK, on the surface of osteoclasts and their precursors. This regulates the differentiation of precursors into multinucleated osteoclasts and osteoclast activation and survival both normally and in most pathologic conditions associated with increased bone resorption. Osteoprotegerin (OPG) is secreted by osteoblasts and osteogenic stromal stem cells and protects the skeleton from excessive bone resorption by binding to RANKL and preventing it from interacting with RANK. The RANKL/OPG ratio in bone marrow is thus an important determinant of bone mass in normal and disease states. RANKL/RANK signaling also regulates lymph node formation and mammary gland lactational hyperplasia in mice, and OPG protects large arteries of mice from medial calcification. This article reviews the roles of the RANKL/RANK/OPG system in bone and other tissues.

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The RANKL-RANK-OPG pathway exerts a crucial role in osteoclast differentiation and bone resorption.
“It has been shown that the receptor activator of nuclear factor-kappa B ligand (RANKL)-RANK-osteoprotegerin (OPG) (RANKL-RANK-OPG) pathway exerts a crucial role in osteoclast differentiation and bone resorption [87,88,89].”
From An Overlooked Bone Metabolic Disorder: Cigarette Smoking-Induced Osteoporosis (2022) · cites this paper as [87]

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Biology of RANK, RANKL, and osteoprotegerin
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Self-citation
Review Biology of RANK, RANKL, and osteoprotegerin
Boyce, B. F., & Xing, L. (2007)
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Functions of RANKL/RANK/OPG in bone modeling and remodeling
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Receptor activator of nuclear factor-κB ligand (RANKL)/RANK/osteoprotegerin system in bone and other tissues (Review)
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Authors: Boyce, B. F., & Xing, L.
Affiliations: University of Rochester Medicine (US)
Corresponding author: Boyce, Brendan F.
ORCID: Boyce, Brendan F.
Xing, Lianping
Venue: Current Osteoporosis Reports
Publisher: Springer Science and Business Media LLC
Published: 2007-09
Volume: 5
Issue: 3
Pages: 98-104
ISSN: 1544-1873 (ISSN-L)
1544-2241
DOI: 10.1007/s11914-007-0024-y
OpenAlex: W2055590859
Cited by: 339
References: 48
Citations by year: 2026: 18 · 2025: 22 · 2024: 32 · 2023: 29 · 2022: 30 · 2021: 26 · 2020: 31 · 2019: 21 · 2018: 24 · 2017: 25 · 2016: 20 · 2015: 17 · 2014: 4 · 2013: 8 · 2012: 5
FWCI: 2.65
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
Locations: Current Osteoporosis Reports (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone health and osteoporosis research
Health Sciences › Medicine › Rheumatology › Osteomyelitis and Bone Disorders Research
Keywords: RANK/RANKL/OPG pathway, osteoclastogenesis, osteoclast activation, bone resorption, osteoblasts, stromal stem cells, RANKL/OPG ratio, bone mass regulation, vascular calcification, NF-κB signaling
MeSH terms: Humans, Osteoclasts, Osteoporosis, Osteoprotegerin, RANK Ligand, Receptor Activator of Nuclear Factor-kappa B

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