The DOI matches its Crossref record; 40 of the 41 references it cites were found in a registry or an index.
Negative regulation of osteoclastogenesis by ectodomain shedding of receptor activator of NF-κB ligand.
Open accessAbstract
Receptor activator of NF-kappaB ligand (RANKL) is a transmembrane glycoprotein that has an essential role in the development of osteoclasts. The extracellular portion of RANKL is cleaved proteolytically to produce soluble RANKL, but definite RANKL sheddase(s) and the physiologic function of RANKL shedding have not yet been determined. In the present study, we found that matrix metalloproteinase (MMP) 14 and a disintegrin and metalloproteinase (ADAM) 10 have strong RANKL shedding activity. In Western blot analysis, soluble RANKL was detected as two different molecular weight products, and RNA interference of MMP14 and ADAM10 resulted in a reduction of both the lower and higher molecular weight products. Suppression of MMP14 in primary osteoblasts increased membrane-bound RANKL and promoted osteoclastogenesis in cocultures with macrophages. Soluble RANKL produced by osteoblasts from MMP14-deficient mice was markedly reduced, and their osteoclastogenic activity was promoted, consistent with the findings of increased osteoclastogenesis in vivo. RANKL shedding is an important process that down-regulates local osteoclastogenesis.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“There are at least three forms of RANKL, two of which possess a transmembrane domain that positions the biologically active carboxy-terminus to the extracellular domain (i.e., a type II transmembrane protein) (Fig. 2).One of these forms, RANKL2, is a shorter alternative splicing variant of RANKL1 (44).Both of these variants can remain on cell surfaces or can be proteolytically cleaved into soluble”
From Receptor Activator of Nuclear Factor κB Ligand and Osteoprotegerin Regulation of Bone Remodeling in Health and Disease (2008) · cites this paper as [45]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
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
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
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
A metalloproteinase disintegrin that releases tumour-necrosis factor-α from cells
Black, R. A., Rauch, C. T., Kozlosky, C. J., Peschon, J. J., Slack, J. L., Wolfson, M. F., Castner, B. J., Stocking, K. L., Reddy, P., Srinivasan, S., et al. (1997) · Nature · doi:10.1038/385729a0 · Cited by 3,149
Takayanagi, H., Kim, S., Koga, T., Nishina, H., Isshiki, M., Yoshida, H., Saiura, A., Isobe, M., Yokochi, T., Inoue, J.-I., et al. (2002) · Developmental Cell · doi:10.1016/s1534-5807(02)00369-6 · Cited by 2,701
A matrix metalloproteinase expressed on the surface of invasive tumour cells
Sato, H., Takino, T., Okada, Y., Cao, J. P., Shinagawa, A., Yamamoto, E., & Seiki, M. (1994) · Nature · doi:10.1038/370061a0 · Cited by 2,534
Self-citationOsteoprotegerin-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
A homologue of the TNF receptor and its ligand enhance T-cell growth and dendritic-cell function.
Anderson, D. M., Maraskovsky, E., Billingsley, W. L., Dougall, W. C., Tometsko, M. E., Roux, E. R., Teepe, M. C., DuBose, R. F., Cosman, D., & Galibert, L. (1997) · Nature · doi:10.1038/36593 · Cited by 2,290
Kong, Y.-Y., Feige, U., Sarosi, I., Bolon, B., Tafuri, A., Morony, S., Capparelli, C., Li, J., Elliott, R., McCabe, S., et al. (1999) · Nature · doi:10.1038/46303 · Cited by 1,856
Prenzel, N., Zwick, E., Daub, H., Leserer, M., Abraham, R., Wallasch, C., & Ullrich, A. (1999) · Nature · doi:10.1038/47260 · Cited by 1,507
RANK is essential for osteoclast and lymph node development.
Dougall, W. C., Glaccum, M., Charrier, K., Rohrbach, K., Brasel, K., De Smedt, T., Daro, E., Smith, J., Tometsko, M. E., Maliszewski, C. R., et al. (1999) · Genes & Development · doi:10.1101/gad.13.18.2412 · Cited by 1,478
Holmbeck, K., Bianco, P., Caterina, J., Yamada, S., Kromer, M., Kuznetsov, S. A., Mankani, M., Gehron Robey, P., Poole, A. R., Pidoux, I., et al. (1999) · Cell · doi:10.1016/s0092-8674(00)80064-1 · Cited by 1,298
Kriegler, M., Perez, C. F., DeFay, K., Albert, I., & Lu, S.-D. (1988) · Cell · doi:10.1016/0092-8674(88)90486-2 · Cited by 1,090
Wong, B. R., Rho, J., Arron, J. R., Robinson, E. A., Orlinick, J. R., Chao, M. V., Kalachikov, S. M., Cayani, E., Bartlett, F. S., Frankel, W. N., et al. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.40.25190 · Cited by 1,042
OSTEOBLASTIC CELLS ARE INVOLVED IN OSTEOCLAST FORMATION
Takahashi, N., Akatsu, T., Udagawa, N., Sasaki, T., Yamaguchi, A., Moseley, J. M., Martin, T. J., & Suda, T. (1988) · Endocrinology · doi:10.1210/endo-123-5-2600 · Cited by 934
Schneider, P., Holler, N., Bodmer, J.-L., Hahne, M., Frei, K., Fontana, A., & Tschopp, J. (1998) · The Journal of Experimental Medicine · doi:10.1084/jem.187.8.1205 · Cited by 827
Harris, R. C. (2003) · Experimental Cell Research · doi:10.1016/s0014-4827(02)00105-2 · Cited by 802
Hartmann, D. (2002) · Human Molecular Genetics · doi:10.1093/hmg/11.21.2615 · Cited by 680
Inada, M., Wang, Y., Byrne, M. H., Rahman, M. U., Miyaura, C., López-Otı́n, C., & Krane, S. M. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0407788101 · Cited by 576
Nakashima, T., Kobayashi, Y., Yamasaki, S., Kawakami, A., Eguchi, K., Sasaki, H., & Sakai, H. (2000) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.2000.3379 · Cited by 508
Takino, T., Sato, H., Shinagawa, A., & Seiki, M. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.39.23013 · Cited by 471
Self-citationThe TRAF Family of Signal Transducers Mediates NF-κB Activation by the TRANCE Receptor
Wong, B. R., Josien, R., Lee, S. Y., Vologodskaia, M., Steinman, R. M., & Choi, Y. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.43.28355 · Cited by 458
Lum, L., Wong, B. R., Josien, R., Becherer, J. D., Erdjument‐Bromage, H., Schlöndorff, J. S., Tempst, P., Choi, Y., & Blobel, C. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.19.13613 · Cited by 412
MMP-7 promotes prostate cancer-induced osteolysis via the solubilization of RANKL
Lynch, C. C., Hikosaka, A., Acuff, H. B., Martin, M. D., Kawai, N., Singh, R. K., Vargo-Gogola, T. C., Begtrup, J. L., Peterson, T. E., Fingleton, B., et al. (2005) · Cancer Cell · doi:10.1016/j.ccr.2005.04.013 · Cited by 402
Tanaka, S., Nakamura, K., Takahasi, N., & Suda, T. (2005) · Immunological Reviews · doi:10.1111/j.0105-2896.2005.00327.x · Cited by 325
Self-citationMiyamori, H., Takino, T., Kobayashi, Y., Tokai, H., Itoh, Y., Seiki, M., & Sato, H. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m103083200 · Cited by 228
Self-citation[20] Role of 1α,25-dihydroxyvitamin D3 in osteoclast differentiation and function
Suda, T., Jimi, E., Nakamura, I., & Takahashi, N. (1997) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/s0076-6879(97)82110-6 · Cited by 186
Itoh, Y., Kajita, M., Kinoh, H., Mori, H., Okada, A., & Seiki, M. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.48.34260 · Cited by 168
Self-citationKojima, S., Itoh, Y., Matsumoto, S., Masuho, Y., & Seiki, M. (2000) · FEBS Letters · doi:10.1016/s0014-5793(00)01919-0 · Cited by 138
Self-citationSchlöndorff, J. S., Lum, L., & Blobel, C. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m010741200 · Cited by 130
Catalytic Properties of ADAM19
Chesneau, V., Becherer, J. D., Zheng, Y., Erdjument‐Bromage, H., Tempst, P., & Blobel, C. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m302781200 · Cited by 129
New experimental approaches in retrovirus-mediated expression screening.
Kitamura (1998) · International Journal of Hematology · doi:10.1016/s0925-5710(98)00025-5 · Cited by 126
Ohtake, Y., Tojo, H., & Seiki, M. (2006) · Journal of Cell Science · doi:10.1242/jcs.03158 · Cited by 125
Self-citationSignal transduction pathways regulating osteoclast differentiation and function
Tanaka, S., Nakamura, I., Inoue, J., Oda, H., & Nakamura, K. (2003) · Journal of Bone and Mineral Metabolism · doi:10.1007/s007740300021 · Cited by 89
Self-citationYamamoto, A., Miyazaki, T., Kadono, Y., Takayanagi, H., Miura, T., Nishina, H., Katada, T., Wakabayashi, K., Oda, H., Nakamura, K., et al. (2002) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.2002.17.4.612 · Cited by 85
Self-citationIshikawa, T., Nishigaki, F., Miyata, S., Hirayama, Y., Minoura, K., Imanishi, J., Neya, M., Mizutani, T., Imamura, Y., Naritomi, Y., et al. (2004) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0706054 · Cited by 61
Isolation of a mouse MT2‐MMP gene from a lung cDNA library and identification of its product
Tanaka, M., Sato, H., Takino, T., Iwata, K., Inoue, M., & Seiki, M. (1997) · FEBS Letters · doi:10.1016/s0014-5793(96)01537-2 · Cited by 56
Self-citationHikita, A., Kadono, Y., Chikuda, H., Fukuda, A., Wakeyama, H., Yasuda, H., Nakamura, K., Oda, H., Miyazaki, T., & Tanaka, S. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m507000200 · Cited by 31
Self-citationIshikawa, T., Nishigaki, F., Miyata, S., Hirayama, Y., Minoura, K., Imanishi, J., Neya, M., Mizutani, T., Imamura, Y., Ohkubo, Y., et al. (2005) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2004.12.014 · Cited by 26
Guo, L., Xie, H., Zhou, H., Luo, X., Peng, Y., & Liao, E. (2004) · Endocrine Research · doi:10.1081/erc-200033719 · Cited by 15
Flagged first, then by citations
1 of the 41 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Osteoimmunology: shared mechanisms and crosstalk between the immune and bone systems
Takayanagi, H. (2007) · Nature Reviews Immunology · doi:10.1038/nri2062 · Cited by 1,878
Functions of RANKL/RANK/OPG in bone modeling and remodeling
Boyce, B. F., & Xing, L. (2008) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2008.03.018 · Cited by 1,844
Edwards, D. R., Handsley, M. M., & Pennington, C. (2008) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2008.08.001 · Cited by 1,163
Biology of RANK, RANKL, and osteoprotegerin
Boyce, B. F., & Xing, L. (2007) · Arthritis Research & Therapy · doi:10.1186/ar2165 · Cited by 994
Kearns, A. E., Khosla, S., & Kostenuik, P. J. (2008) · Endocrine Reviews · doi:10.1210/er.2007-0014 · Cited by 824
Metadata
- Authors
- Hikita, A., Yana, I., Wakeyama, H., Nakamura, M., Kadono, Y., Oshima, Y., Nakamura, K., Seiki, M., & Tanaka, S.
- Affiliations
- The University of Tokyo (JP)
- Institute of Medical Science, The University of Tokyo (JP)
- Corresponding author
- Tanaka, Sakae
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2006-12
- Volume
- 281
- Issue
- 48
- Pages
- 36846-36855
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W1999201913
- Cited by
- 236
- References
- 41
- Citations by year
- 2026: 6 · 2025: 4 · 2024: 8 · 2023: 15 · 2022: 7 · 2021: 13 · 2020: 15 · 2019: 8 · 2018: 13 · 2017: 17 · 2016: 7 · 2015: 10 · 2014: 9 · 2013: 8 · 2012: 12
- FWCI
- 6.66
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Protease and Inhibitor Mechanisms
- Health Sciences › Medicine › Rheumatology › Rheumatoid Arthritis Research and Therapies
- Keywords
- RANKL, ectodomain shedding, osteoclastogenesis, MMP-14, ADAM10, soluble RANKL, osteoblasts
- MeSH terms
- ADAM10 Protein, Animals, Binding Sites, Bone Diseases, Metabolic, Bone Marrow, Humans, Macrophages, Membrane Proteins, Mice, Inbred C57BL, Osteoblasts, Osteoclasts, Down-Regulation, Coculture Techniques, Mice, ADAM Proteins, RANK Ligand, Matrix Metalloproteinase 14, Amyloid Precursor Protein Secretases
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
