Expression of RANKL and OPG correlates with age-related bone loss in male C57BL/6 mice.
Open accessAbstract
Osteoblasts regulate the recruitment and activity of osteoclasts through expression of RANKL and osteoprotegerin (OPG). To determine whether expression of RANKL and OPG change with age and how these changes relate to the bone loss of aging, we measured bone mass and cancellous volume, and expression of RANKL, OPG, alkaline phosphatase (AP), osteocalcin (OC), and alpha I collagen (COLL) in whole bone and osteoblast-like cells in culture using 6-week- (young), 6-month- (adult), and 24-month-old (old) mice. Cancellous volume decreased by 20% from young to adult and by 52% from adult to old. RANKL mRNA levels in whole bone were 2.1-fold and 4.4-fold higher in adult and old mice, respectively, compared with young mice, whereas OPG mRNA levels decreased with age slightly. RANKL expression was negatively (r = −0.99) and OPG was positively (r = 0.92) correlated with cancellous bone volume. Expression of RANKL was higher and OPG lower in cells from older animals early in culture (day 7). With cell maturation, RANKL mRNA levels in cells from young and adult mice increased, whereas levels in cells from old animals decreased. By 21 and 28 days of culture, no differences were found in RANKL mRNA in osteoblast-like cells among different age groups. We conclude that expression of RANKL and OPG change with age in whole bone and in cultured osteoblast-like cells. These changes favor increased osteoclast over osteoblast activity, and may explain, in part, the imbalance in bone formation and resorption associated with aging.
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Osteoclast activity likely depends at least in part on the relative balance between RANKL and OPG.
“Osteoclast activity is likely to depend, at least in part, on the relative balance of RANKL and OPG.”
From Receptor Activator of Nuclear Factor κB Ligand and Osteoprotegerin Regulation of Bone Remodeling in Health and Disease (2008) · cites this paper as [89]
Age-related bone loss in normal mice correlates with increased skeletal RANKL mRNA and reduced OPG expression.
“Interestingly, the typical age-related bone loss seen in normal mice was correlated with increased skeletal expression of RANKL mRNA and reduced expression of OPG (89).”
From Receptor Activator of Nuclear Factor κB Ligand and Osteoprotegerin Regulation of Bone Remodeling in Health and Disease (2008) · cites this paper as [89]
Cancellous bone volume drops precipitously with aging in normal mice.
“Cancellous bone volume drops precipitously with aging in normal mice (89)”
From Receptor Activator of Nuclear Factor κB Ligand and Osteoprotegerin Regulation of Bone Remodeling in Health and Disease (2008) · cites this paper as [89]
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Cites
Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation.
Lacey, D. L., Timms, E., Tan, H.-L., Kelley, M. J., Dunstan, C. R., Burgess, T., Elliott, R., Colombero, A., Elliott, G., Scully, S., et al. (1998) · Cell · doi:10.1016/s0092-8674(00)81569-x · Cited by 5,439 · see citing works
Osteoprotegerin: a novel secreted protein involved in the regulation of bone density.
Simonet, W. S., Lacey, D. L., Dunstan, C. R., Kelley, M., Chang, M.-S., Lüthy, R., Nguyen, H. Q., Wooden, S., Bennett, L., Boone, T., et al. (1997) · Cell · doi:10.1016/s0092-8674(00)80209-3 · Cited by 5,130 · see citing works
Yasuda, H., Shima, N., Nakagawa, N., Yamaguchi, K., Kinosaki, M., Mochizuki, S.-I., Tomoyasu, A., Yano, K., Goto, M., Murakami, A., et al. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.7.3597 · Cited by 4,224 · see citing works
OPGL is a key regulator of osteoclastogenesis, lymphocyte development and lymph node organogenesis.
Kong, Y.-Y., Yoshida, H., Sarosi, I., Tan, H.-L., Timms, E., Capparelli, C., Morony, S., Oliveira-dos-Santos, A. J., Van, G., Itie, A., et al. (1999) · Nature · doi:10.1038/16852 · Cited by 3,351 · see citing works
Osteoprotegerin-deficient mice develop early onset osteoporosis and arterial calcification.
Bucay, N., Sarosi, I., Dunstan, C. R., Morony, S., Tarpley, J., Capparelli, C., Scully, S., Tan, H. L., Xu, W., Lacey, D. L., et al. (1998) · Genes & Development · doi:10.1101/gad.12.9.1260 · Cited by 2,483 · see citing works
Yasuda, H., Shima, N., Nakagawa, N., Mochizuki, S.-I., Yano, K., Fujise, N., Sato, Y., Goto, M., Yamaguchi, K., Kuriyama, M., et al. (1998) · Endocrinology · doi:10.1210/endo.139.3.5837 · Cited by 1,201 · see citing works
Severe osteoporosis in mice lacking osteoclastogenesis inhibitory factor/osteoprotegerin.
Mizuno, A., Amizuka, N., Irie, K., Murakami, A., Fujise, N., Kanno, T., Sato, Y., Nakagawa, N., Yasuda, H., Mochizuki, S.-I., et al. (1998) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1998.8697 · Cited by 775 · see citing works
The ligand for osteoprotegerin (OPGL) directly activates mature osteoclasts.
Burgess, T. L., Qian, Y.-X., Kaufman, S., Ring, B. D., Van, G., Capparelli, C., Kelley, M., Hsu, H., Boyle, W. J., Dunstan, C. R., et al. (1999) · The Journal of Cell Biology · doi:10.1083/jcb.145.3.527 · Cited by 689 · see citing works
Yasuda, H., Shima, N., Nakagawa, N., Yamaguchi, K., Kinosaki, M., Mochizuki, S.-I., Tomoyasu, A., Yano, K., Goto, M., Murakami, A., et al. (1998) · Cited by 650 · see citing works
Browner, W. S., Lui, L., & Cummings, S. R. (2001) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.86.2.7192 · Cited by 529 · see citing works
Lee, S.-K., & Lorenzo, J. A. (1999) · Endocrinology · doi:10.1210/endo.140.8.6887 · Cited by 464 · see citing works
Yano, K., Tsuda, E., Washida, N., Kobayashi, F., Goto, M., Harada, A., Ikeda, K., Higashio, K., & Yamada, Y. (1999) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.1999.14.4.518 · Cited by 363 · see citing works
Changes in Bone Structure and Mass With Advancing Age in the Male C57BL/6J Mouse
Halloran, B. P., Ferguson, V. L., Simske, S. J., Burghardt, A. J., Venton, L. L., & Majumdar, S. (2002) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.2002.17.6.1044 · Cited by 302 · see citing works
Self-citationGori, F., Hofbauer, L. C., Dunstan, C. R., Spelsberg, T. C., Khosla, S., & Riggs, B. L. (2000) · Endocrinology · doi:10.1210/endo.141.12.7840 · Cited by 297 · see citing works
Tan, K. B., Harrop, J., Reddy, M. P., Young, P. R., Terrett, J. A., Emery, J. G., Moore, G. P., & Truneh, A. (1997) · Gene · doi:10.1016/s0378-1119(97)00509-x · Cited by 277 · see citing works
Osteoprotegerin Serum Levels in Men: Correlation with Age, Estrogen, and Testosterone Status
Szulc, P., Hofbauer, L. C., Heufelder, A. E., Roth, S., & Delmas, P. D. (2001) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.86.7.7657 · Cited by 250 · see citing works
Osteoprotegerin A Physiological and Pharmacological Inhibitor of Bone Resorption.
Kostenuik, P. J., & Shalhoub, V. (2001) · Current Pharmaceutical Design · doi:10.2174/1381612013397807 · Cited by 224 · see citing works
The Skeletal Structure of Insulin-Like Growth Factor I-Deficient Mice
Bikle, D. D., Majumdar, S., Laib, A., Powell-Braxton, L., Rosen, C. J., Beamer, W. G., Nauman, E. A., Leary, C., & Halloran, B. P. (2001) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.2001.16.12.2320 · Cited by 196 · see citing works
Self-citationFazzalari, N. L., Kuliwaba, J. S., Atkins, G. J., Forwood, M. R., & Findlay, D. M. (2001) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.2001.16.6.1015 · Cited by 129 · see citing works
Onyia, J. E., Miles, R. R., Yang, X., Halladay, D. L., Hale, J. E., GLASEBROOK, A. L., McClure, D. B., Seno, G., Churgay, L. M., Chandrasekhar, S., et al. (2000) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.2000.15.5.863 · Cited by 124 · see citing works
Kostenuik, P. J., Harris, J., Halloran, B. P., Turner, R. T., Morey-Holton, E. R., & Bikle, D. D. (1999) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.1999.14.1.21 · Cited by 119 · see citing works
Self-citationIkeda, T., Utsuyama, M., & Hirokawa, K. (2001) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.2001.16.8.1416 · Cited by 107 · see citing works
Nauman, E. A., Satcher, R. L., Keaveny, T. M., Halloran, B. P., & Bikle, D. D. (2001) · Journal of Applied Physiology · doi:10.1152/jappl.2001.90.5.1849 · Cited by 106 · see citing works
Self-citationMakhluf, H. A., Mueller, S. M., Mizuno, S., & Glowacki, J. (2000) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.2000.2182 · Cited by 96 · see citing works
Osteoporosis: Pathogenesis and Therapy
Avioli, L. V. (1977) · Elsevier eBooks · doi:10.1016/b978-0-12-068701-5.50012-9 · Cited by 77 · see citing works
Age-related bone loss in mice is associated with an increased osteoclast progenitor pool
Perkins, S. L., Gibbons, R., Kling, S. J., & Kahn, A. J. (1994) · Bone · doi:10.1016/8756-3282(94)90893-1 · Cited by 73 · see citing works
Age-related bone loss in lumbar vertebrae of CW-1 female mice: A histomorphometric study
Bar-Shira-Maymon, B., Coleman, R., Cohen, A., et al. (1989) · Calcified Tissue International · doi:10.1007/bf02556238 · Cited by 51 · see citing works
Menkes, C. J. (1997) · Current Opinion in Rheumatology · doi:10.1097/00002281-199707000-00012 · Cited by 26 · see citing works
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Lombard, D. B., Chua, K. F., Mostoslavsky, R., Franco, S., Gostissa, M., & Alt, F. W. (2005) · Cell · doi:10.1016/j.cell.2005.01.028 · Cited by 944 · see citing works
Kearns, A. E., Khosla, S., & Kostenuik, P. J. (2008) · Endocrine Reviews · doi:10.1210/er.2007-0014 · Cited by 824 · see citing works
Osteoprotegerin and RANKL regulate bone resorption, density, geometry and strength.
KOSTENUIK, P. (2005) · Current Opinion in Pharmacology · doi:10.1016/j.coph.2005.06.005 · Cited by 281 · see citing works
Tsangari, H., Findlay, D. M., Kuliwaba, J. S., Atkins, G. J., & Fazzalari, N. L. (2004) · Bone · doi:10.1016/j.bone.2004.02.006 · Cited by 69 · see citing works
Brennan, T. A., Egan, K. P., Lindborg, C. M., Chen, Q., Sweetwyne, M. T., Hankenson, K. D., Xie, S. X., Johnson, F. B., & Pignolo, R. J. (2014) · Disease Models & Mechanisms · doi:10.1242/dmm.014928 · Cited by 45 · see citing works
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Lee, S. Y., Fam, K. D., Chia, K. L., Yap, M. M. C., Goh, J., Yeo, K. P., Yap, E. P. H., Chotirmall, S. H., & Lim, C. L. (2020) · Experimental Physiology · doi:10.1113/ep088351 · Cited by 24 · see citing works
- Authors
- Cao, J., Venton, L., Sakata, T., & Halloran, B. P.
- Affiliations
- San Francisco VA Medical Center (US)
- Corresponding author
- Halloran, Bernard P
- Venue
- Journal of Bone and Mineral Research
- Publisher
- Oxford University Press (OUP)
- Published
- 2003-02-01
- Volume
- 18
- Issue
- 2
- Pages
- 270-277
- ISSN
- 0884-0431 (ISSN-L)
- 1523-4681
- OpenAlex
- W1983577624
- Cited by
- 173
- References
- 28
- Citations by year
- 2026: 2 · 2025: 10 · 2024: 12 · 2023: 13 · 2022: 6 · 2021: 6 · 2020: 12 · 2019: 6 · 2018: 2 · 2017: 3 · 2016: 6 · 2015: 7 · 2014: 5 · 2013: 3 · 2012: 7
- FWCI
- 2.76
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
- Locations
- Journal of Bone and Mineral Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute of Diabetes and Digestive and Kidney Diseases (DK07418-21, T32DK007418)
- 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 › Bone and Dental Protein Studies
- Keywords
- RANKL, osteoprotegerin, age-related bone loss, bone aging, osteoblasts, osteoclasts, cancellous bone volume, bone mass, osteoblast-like cells, osteogenic differentiation, bone formation and resorption, C57BL/6 mice
- MeSH terms
- Aging, Animals, Body Weight, Bone and Bones, Carrier Proteins, Cells, Cultured, Glycoproteins, Male, Membrane Glycoproteins, Mice, Inbred C57BL, Osteoblasts, Osteoporosis, RNA, Messenger, Time Factors, Blotting, Western, Receptors, Tumor Necrosis Factor, Receptors, Cytoplasmic and Nuclear, Reverse Transcriptase Polymerase Chain Reaction, Mice, Osteoprotegerin, RANK Ligand, Receptor Activator of Nuclear Factor-kappa B
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