Cited by 129Bone Metabolism and DiseasesBone health and osteoporosis researchRheumatoid Arthritis Research and Therapies

The Ratio of Messenger RNA Levels of Receptor Activator of Nuclear Factor κB Ligand to Osteoprotegerin Correlates with Bone Remodeling Indices in Normal Human Cancellous Bone but Not in Osteoarthritis

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Fazzalari, Nicola L., Kuliwaba, Julia S., Atkins, Gerald J., Forwood, Mark R., Findlay, David M.·2001·Journal of Bone and Mineral Research

Abstract

The determinants of cancellous bone turnover and trabecular structure are not understood in normal bone or skeletal disease. Bone remodeling is initiated by osteoclastic resorption followed by osteoblastic formation of new bone. Receptor activator of nuclear factor κB ligand (RANKL) is a newly described regulator of osteoclast formation and function, the activity of which appears to be a balance between interaction with its receptor RANK and with an antagonist binding protein osteoprotegerin (OPG). Therefore, we have examined the relationship between the expression of RANKL, RANK, and OPG and indices of bone structure and turnover in human cancellous bone from the proximal femur. Bone samples were obtained from individuals with osteoarthritis (OA) at joint replacement surgery and from autopsy controls. Histomorphometric analysis of these samples showed that eroded surface (ES/BS) and osteoid surface (OS/BS) were positively associated in both control (p < 0.001) and OA (p < 0.02), indicating that the processes of bone resorption and bone formation remain coupled in OA, as they are in controls. RANKL, OPG, and RANK messenger RNA (mRNA) were abundant in human cancellous bone, with significant differences between control and OA individuals. In coplotting the molecular and histomorphometric data, strong associations were found between the ratio of RANKL/OPG mRNA and the indices of bone turnover (RANKL/OPG vs. ES/BS: r = 0.93, p < 0.001; RANKL/OPG vs. OS/BS: r = 0.80, p < 0.001). These relationships were not evident in trabecular bone from severe OA, suggesting that bone turnover may be regulated differently in this disease. We propose that the effective concentration of RANKL is related causally to bone turnover.

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Authors
Fazzalari, N. L., Kuliwaba, J. S., Atkins, G. J., Forwood, M. R., & Findlay, D. M.
Affiliations
  • South Australia Pathology (AU)
  • Royal Adelaide Hospital (AU)
  • The University of Queensland (AU)
Corresponding author
Fazzalari, Nicola L.
Venue
Journal of Bone and Mineral Research
Published
2001-06-01
Volume
16
Issue
6
Pages
1015-1027
ISSN
  • 0884-0431 (ISSN-L)
  • 1523-4681
OpenAlex
W2019917228
Cited by
129
References
34
Citations by year
2025: 3 · 2024: 2 · 2023: 1 · 2022: 4 · 2021: 1 · 2020: 4 · 2019: 4 · 2018: 3 · 2017: 2 · 2016: 1 · 2015: 3 · 2014: 3 · 2013: 6 · 2012: 5
FWCI
2.21
Type
journal article
Language
en
Open access
Locations
  • Journal of Bone and Mineral Research (publishedVersion)
  • PubMed (publishedVersion)
  • Adelaide Research & Scholarship (AR&S) (University of Adelaide) (submittedVersion)
  • UCL Discovery (University College London) (submittedVersion)
Funders
  • Arthritis Foundation
  • Arthritis Foundation of Australia
  • Royal Adelaide Hospital
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 › Rheumatoid Arthritis Research and Therapies
Keywords
RANKL, osteoprotegerin, RANK, bone remodeling, bone turnover, osteoarthritis, trabecular bone, osteoclastogenesis, mRNA expression, histomorphometry, proximal femur, bone resorption, bone formation
MeSH terms
Adult, Age Factors, Aged, Aged, 80 and over, Carrier Proteins, Female, Femur, Glycoproteins, Humans, Male, Membrane Glycoproteins, Middle Aged, Osteoarthritis, Reference Values, RNA, Messenger, Gene Expression, Case-Control Studies, Bone Remodeling, Receptors, Tumor Necrosis Factor, Receptors, Cytoplasmic and Nuclear, Osteoprotegerin, RANK Ligand, Receptor Activator of Nuclear Factor-kappa B

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