Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/6787
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Type: Journal article
Title: The ratio of messenger RNA levels of receptor activator of nuclear factor kB ligand to osteoprotegerin correlates with bone remodeling indices in normal human cancellous bone but not in osteoarthritis
Author: Fazzalari, N.
Kuliwaba, J.
Atkins, G.
Forwood, M.
Findlay, D.
Citation: Journal of Bone and Mineral Research, 2001; 16(6):1015-1027
Publisher: Amer Soc Bone & Mineral Res
Issue Date: 2001
ISSN: 0884-0431
1523-4681
Statement of
Responsibility: 
Nicola L. Fazzalari, Julia S. Kuliwaba, Gerald J. Atkins, Mark R. Forwood, and David M. Findlay
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.
Keywords: Femur; Humans; Osteoarthritis; Glycoproteins; Carrier Proteins; Membrane Glycoproteins; Receptors, Tumor Necrosis Factor; Receptors, Cytoplasmic and Nuclear; RNA, Messenger; Case-Control Studies; Age Factors; Bone Remodeling; Gene Expression; Reference Values; Adult; Aged; Aged, 80 and over; Middle Aged; Female; Male; RANK Ligand; Receptor Activator of Nuclear Factor-kappa B; Osteoprotegerin
Description: © by the American Society for Bone and Mineral Research.
RMID: 0020010873
DOI: 10.1359/jbmr.2001.16.6.1015
Appears in Collections:Orthopaedics and Trauma publications

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