The DOI matches its Crossref record; 53 of the 53 references it cites were found in a registry or an index.
Calcitonin-gene-related peptide stimulates stromal cell osteogenic differentiation and inhibits RANKL induced NF-κB activation, osteoclastogenesis and bone resorption
Open accessAbstract
Previously we observed that capsaicin treatment in rats inhibited sensory neuropeptide signaling, with a concurrent reduction in trabecular bone formation and bone volume, and an increase in osteoclast numbers and bone resorption. Calcitonin gene-related peptide (CGRP) is a neuropeptide richly distributed in sensory neurons innervating the skeleton and we postulated that CGRP signaling regulates bone integrity. In this study we examined CGRP effects on stromal and bone cell differentiation and activity in vitro. CGRP receptors were detected by immunocytochemical staining and real time PCR assays in mouse bone marrow stromal cells (BMSCs) and bone marrow macrophages (BMMs). CGRP effects on BMSC proliferation and osteoblastic differentiation were studied using BrdU incorporation, PCR products, alkaline phosphatase (ALP) activity, and mineralization assays. CGRP effects on BMM osteoclastic differentiation and activity were determined by quantifying tartrate-resistant acid phosphatase positive (TRAP+) multinucleated cells, pit erosion area, mRNA levels of TRAP and cathepsin K, and nuclear factor-κB (NF-κB) nuclear localization. BMSCs, osteoblasts, BMMs, and osteoclasts all expressed CGRP receptors. CGRP (10-10-10-8M) stimulated BMSC proliferation, up-regulated the expression of osteoblastic genes, and increased ALP activity and mineralization in the BMSCs. In BMM cultures CGRP (10-8M) inhibited receptor activator of NF-κB ligand (RANKL) activation of NF-κB. CGRP also down-regulated osteoclastic genes like TRAP and cathepsin K, decreased the numbers of TRAP+ cells, and inhibited bone resorption activity in RANKL stimulated BMMs. These results suggest that CGRP signaling maintains bone mass both by directly stimulating stromal cell osteoblastic differentiation and by inhibiting RANKL induced NF-κB activation, osteoclastogenesis, and bone resorption.
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?
The cited source says what the claim attributes to it.
In the citing paper
“suggesting that CGRP acts with higher potency to inhibit osteoclast activity than osteoclast differentiation (213).”
From The Activity of Peptides of the Calcitonin Family in Bone (2019) · cites this paper as [213]
The cited source says what the claim attributes to it.
In the citing paper
“In cells cultured from mouse bone marrow and induced to differentiate into osteoclasts by M-CSF and RANKL, the area of resorption pits was reduced by CGRP in a concentration of 0.1 nM or higher, whereas higher concentrations of 10 nM CGRP were required for the inhibition of TRAP-positive cell formation”
From The Activity of Peptides of the Calcitonin Family in Bone (2019) · cites this paper as [213]
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
RAMPs regulate the transport and ligand specificity of the calcitonin-receptor-like receptor
McLatchie, L. M., Fraser, N. J., Main, M. J., Wise, A., Brown, J., Thompson, N., Solari, R., Lee, M. G., & Foord, S. M. (1998) · Nature · doi:10.1038/30666 · Cited by 2,134
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
Minireview: The OPG/RANKL/RANK System
Khosla, S. (2001) · Endocrinology · doi:10.1210/endo.142.12.8536 · Cited by 1,515
Origins of skeletal pain: sensory and sympathetic innervation of the mouse femur
Mach, D. B., Rogers, S. D., Sabino, M. C., Luger, N. M., Schwei, M. J., Pomonis, J. D., Keyser, C. P., Clohisy, D. R., Adams, D. J., O’Leary, P., et al. (2002) · Neuroscience · doi:10.1016/s0306-4522(02)00165-3 · Cited by 676
Rapidly Forming Apatitic Mineral in an Osteoblastic Cell Line (UMR 106—01 BSP)
Stanford, C. M., Jacobson, P. A., Eanes, E. D., Lembke, L. A., & Midura, R. J. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.16.9420 · Cited by 439
Austin, L. A., & Heath, H. (1981) · New England Journal of Medicine · doi:10.1056/nejm198101293040505 · Cited by 417
Substance P- and CGRP-immunoreactive nerves in bone
Bjurholm, A., Andris Kreicbergs, A., Brodin, E., & Schultzberg, M. (1988) · Peptides · doi:10.1016/0196-9781(88)90023-x · Cited by 384
Huhtakangas, J. A., Olivera, C. J., Bishop, J. E., Zanello, L. P., & Norman, A. W. (2004) · Molecular Endocrinology · doi:10.1210/me.2004-0116 · Cited by 337
Gamse, R., Leeman, S. E., Holzer, P. D., & Lembeck, F. (1981) · Naunyn-Schmiedeberg s Archives of Pharmacology · doi:10.1007/bf00500070 · Cited by 316
Shui, C., Spelsberg, T. C., Riggs, B. L., & Khosla, S. (2003) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.2003.18.2.213 · Cited by 231
Togari, A., Arai, M., Mizutani, S., Mizutani, S., Koshihara, Y., & Nagatsu, T. (1997) · Neuroscience Letters · doi:10.1016/s0304-3940(97)00649-6 · Cited by 206
Decreased Bone Formation and Osteopenia in Mice Lacking α-Calcitonin Gene-Related Peptide
Schinke, T., Liese, S., Priemel, M., Haberland, M., Schilling, A. F., Catala-Lehnen, P., Blicharski, D., Rueger, J. M., Gagel, R. F., Emeson, R. B., et al. (2004) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.040915 · Cited by 177
Capsaicin-Sensitive Sensory Neurons Contribute to the Maintenance of Trabecular Bone Integrity
Offley, S. C., Guo, T., Wei, T., Clark, J. D., Vogel, H. S., Lindsey, D. P., Jacobs, C. R., Yao, W., Lane, N. E., & Kingery, W. S. (2005) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.041108 · Cited by 175
Self-citationEffects of calcitonin, amylin, and calcitonin gene-related peptide on osteoclast development
Cornish, J., Callon, K. E., Bava, U., Kamona, S. A., Cooper, G. J. S., & Reid, I. R. (2001) · Bone · doi:10.1016/s8756-3282(01)00494-x · Cited by 173
Promoter structure of mouse RANKL/TRANCE/OPGL/ODF gene
Kitazawa, R., Kitazawa, S., & Maeda, S. (1999) · Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression · doi:10.1016/s0167-4781(99)00032-9 · Cited by 153
Dackor, R. T., Fritz-Six, K. L., Dunworth, W. P., Gibbons, C. L., Smithies, O., & Caron, K. M. (2006) · Molecular and Cellular Biology · doi:10.1128/mcb.26.7.2511-2518.2006 · Cited by 146
A New Calcitonin-Receptor-like Sequence in Rat Pulmonary Blood Vessels
Njuki, F., Nicholl, C. G., Howard, A., Mak, J. C. W., Barnes, P. J., Girgis, S. I., & Legon, S. (1993) · Clinical Science · doi:10.1042/cs0850385 · Cited by 142
Targeted Expression of Calcitonin Gene-Related Peptide to Osteoblasts Increases Bone Density in Mice
Ballica, R., Valentijn, K., Khachatryan, A., Guerder, S., Kapadia, S., Gundberg, C., Gilligan, J., Flavell, R. A., & Vignery, A. (1999) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.1999.14.7.1067 · Cited by 133
Comparison of the Effects of Calcitonin Gene-Related Peptide and Amylin on Osteoblasts
Dr. Cornish, J., Callon, K. E., Lin, C. Q., Xiao, C. L., Gamble, G. D., Cooper, G. J. S., & Reid, I. R. (1999) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.1999.14.8.1302 · Cited by 121
Wang, M. W.-H., Shi, W., Faccio, R., Takeshita, S., Tebas, P., Powderly, W. G., Teitelbaum, S. L., & Ross, F. P. (2004) · Journal of Clinical Investigation · doi:10.1172/jci15797 · Cited by 121
Liu, F., Malaval, L., & Aubin, J. E. (2003) · Journal of Cell Science · doi:10.1242/jcs.00376 · Cited by 116
Wuthier, R. E., Chin, J. E., Hale, J. E., Register, T. C., Hale, L. V., & Ishikawa, Y. (1985) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)36354-8 · Cited by 115
Vignery, A., & McCarthy, T. L. (1996) · Bone · doi:10.1016/8756-3282(96)00017-8 · Cited by 101
Amylin inhibits bone resorption by a direct effect on the motility of rat osteoclasts
Alam, A., Moonga, B., Bevis, P., Huang, C., & Zaidi, M. (1993) · Experimental Physiology · doi:10.1113/expphysiol.1993.sp003679 · Cited by 99
Millet, I., Phillips, R. J., Sherwin, R. S., Ghosh, S., Voll, R. E., Flavell, R. A., Vignery, A., & Rincón, M. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.275.20.15114 · Cited by 92
A direct action of human calcitonin gene-related peptide on isolated osteoclasts
Zaidi, M., Chambers, T. J., Das, R., Morris, H. R., & MacIntyre, I. M. (1987) · Journal of Endocrinology · doi:10.1677/joe.0.1150511 · Cited by 92
Effects of calcitonin gene-related peptide on bone turnover in ovariectomized rats
Valentijn, K., Gutow, A. P., Troiano, N., Gundberg, C., Gilligan, J. P., & Vignery, A. (1997) · Bone · doi:10.1016/s8756-3282(97)00142-7 · Cited by 89
Héroux, M., Hogue, M., Lemieux, S., & Bouvier, M. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m701790200 · Cited by 82
Villa, I., Fiume, C. D., Maestroni, A., Rubinacci, A., Ravasi, F., & GUIDOBONO, F. (2003) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00307.2002 · Cited by 82
Calcitonin Deficiency in Mice Progressively Results in High Bone Turnover
Huebner, A. K., Schinke, T., Priemel, M., Schilling, S., Schilling, A. F., Emeson, R. B., Rueger, J. M., & Amling, M. (2006) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.060820 · Cited by 81
Hyaluronan Increases RANKL Expression in Bone Marrow Stromal Cells Through CD44
Cao, J., Singleton, P. A., Majumdar, S., Boudignon, B. M., Burghardt, A. J., Kurimoto, P., Wronski, T. J., Bourguignon, L., & Halloran, B. P. (2005) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.041014 · Cited by 79
Self-citationOwan, I., & Ibaraki, K. (1994) · Bone and Mineral · doi:10.1016/s0169-6009(08)80152-3 · Cited by 76
Michelangeli, V. P., Fletcher, A. E., Allan, E. H., Nicholson, G. C., & Martin, T. J. (1989) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.5650040220 · Cited by 75
Effect of Calcitonin on the Rates of Bone Formation and Resorption in the Rat
Baylink, D. J., Morey, E. R., & RICH, C. (1969) · Endocrinology · doi:10.1210/endo-84-2-261 · Cited by 71
The Sural Nerve in Familial Dysautonomia
Pearson, J., Dancis, J., Axelrod, F. B., & Grover, N. (1975) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/00005072-197509000-00004 · Cited by 71
Villa, I., Mrak, E., Rubinacci, A., Ravasi, F., & GUIDOBONO, F. (2006) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00354.2005 · Cited by 70
Cooper, R. R. (1968) · Science · doi:10.1126/science.160.3825.327 · Cited by 67
Akopian, A., Demulder, A., Ouriaghli, F. E., Corazza, F., Fondu, P., & Bergmann, P. (2000) · Peptides · doi:10.1016/s0196-9781(00)00185-6 · Cited by 64
Effects of calcitonin gene-related peptide and amylin on human osteoblast-like cells proliferation
Villa, I., Melzi, R., Pagani, F., Ravasi, F., Rubinacci, A., & GUIDOBONO, F. (2000) · European Journal of Pharmacology · doi:10.1016/s0014-2999(00)00872-4 · Cited by 62
Kashiba, H., Ueda, Y., & Senba, E. (1996) · Neuroscience · doi:10.1016/s0306-4522(96)00334-x · Cited by 59
Ishizuka, K., Hirukawa, K., Nakamura, H., & Togari, A. (2005) · Neuroscience Letters · doi:10.1016/j.neulet.2004.12.046 · Cited by 57
Granholm, S., Lundberg, P., & Lerner, U. H. (2008) · Journal of Cellular Biochemistry · doi:10.1002/jcb.21674 · Cited by 54
Sohn, S. (2005) · Acta Oto-Laryngologica · doi:10.1080/00016480410017710 · Cited by 48
Towhidul Alam, A. S. M., Moonga, B. S., Bevis, P. J. R., Huang, C. L.-H., & Zaidi, M. (1991) · Biochemical and Biophysical Research Communications · doi:10.1016/0006-291x(91)91345-d · Cited by 46
RAMPs and CRLR expressions in osteoblastic cells after dexamethasone treatment
Uzan, B., de Vernejoul, M.-C., & Cressent, M. (2004) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2004.07.037 · Cited by 43
Bone Mineral Density and Metabolism in Familial Dysautonomia
Maayan, C., Bar‐On, E., Foldes, A. J., Gesundheit, B., & Pollak, R. D. (2002) · Osteoporosis International · doi:10.1007/s001980200050 · Cited by 43
Drissi, H., Hott, M., Marie, P. J., & Lasmoles, F. (1997) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.1997.12.11.1805 · Cited by 43
Kawase, T., Okuda, K., & Burns, D. M. (2005) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00504.2004 · Cited by 33
Kawase, T., Okuda, K., & Burns, D. M. (2003) · European Journal of Pharmacology · doi:10.1016/s0014-2999(03)01763-1 · Cited by 27
bFGF Administration Lowers the Phosphate Threshold for Mineralization in Bone Marrow Stromal Cells
Nauman, E. A., Sakata, T., Keaveny, T. M., Halloran, B. P., & Bikle, D. D. (2003) · Calcified Tissue International · doi:10.1007/s00223-002-1033-6 · Cited by 24
Self-citationMineralization of Adult Mouse Bone Marrow In Vitro
Schoeters, G. E. R., de Saint‐Georges, L., Heuvel, R. V. D., & Vanderborght, O. L. J. (1988) · Cell Proliferation · doi:10.1111/j.1365-2184.1988.tb00794.x · Cited by 19
Nakamura, M., Morimoto, S., Yang, Q., Hisamatsu, T., Hanai, N., Nakamura, Y., Mori, I., & Kakudo, K. (2005) · Journal of Molecular Endocrinology · doi:10.1677/jme.1.01652 · Cited by 19
Calcitonin gene related peptide in familial dysautonomia
Maayan, C., Becker, Y., Gesundheit, B., & Girgis, S. I. (2001) · Neuropeptides · doi:10.1054/npep.2001.0863 · Cited by 15
Flagged first, then by citations
Cited by
Sorted by citations
Lai, N. Y., Musser, M. A., Pinho-Ribeiro, F. A., Baral, P., Jacobson, A. R., Ma, P., Potts, D. E., Chen, Z., Paik, D., Soualhi, S., et al. (2019) · Cell · doi:10.1016/j.cell.2019.11.014 · Cited by 357
Engineering vascularized and innervated bone biomaterials for improved skeletal tissue regeneration
Marrella, A., Lee, T. Y., Lee, D. H., Karuthedom, S., Syla, D., Chawla, A., Khademhosseini, A., & Jang, H. L. (2017) · Materials Today · doi:10.1016/j.mattod.2017.10.005 · Cited by 320
Nerves in Bone: Evolving Concepts in Pain and Anabolism
Brazill, J. M., Beeve, A. T., Craft, C. S., Ivanusic, J. J., & Scheller, E. L. (2019) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.3822 · Cited by 206
Muscle-bone interactions: From experimental models to the clinic? A critical update
Laurent, M. R., Dubois, V., Claessens, F., Verschueren, S., Vanderschueren, D., Gielen, E., & Jardí, F. (2015) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2015.10.017 · Cited by 156
The Activity of Peptides of the Calcitonin Family in Bone
Naot, D., Musson, D. S., & Cornish, J. (2019) · Physiological Reviews · doi:10.1152/physrev.00066.2017 · Cited by 141
Metadata
- Authors
- Wang, L., Shi, X., Zhao, R., Halloran, B. P., Clark, D. J., Jacobs, C. R., & Kingery, W. S.
- Affiliations
- VA Palo Alto Health Care System (US)
- San Francisco VA Medical Center (US)
- Corresponding author
- Wang, Liping
- Venue
- Bone
- Publisher
- Elsevier BV
- Published
- 2010-05
- Volume
- 46
- Issue
- 5
- Pages
- 1369-1379
- ISSN
- 1873-2763 (ISSN-L)
- 8756-3282
- PMC
- PMC2854244
- OpenAlex
- W2039009902
- Semantic Scholar
- 97501e887b43c9d591e6450a3690e83b185845cc
- Cited by
- 198
- References
- 53
- Citations by year
- 2026: 11 · 2025: 17 · 2024: 16 · 2023: 19 · 2022: 16 · 2021: 8 · 2020: 17 · 2019: 18 · 2018: 18 · 2017: 10 · 2016: 7 · 2015: 14 · 2014: 6 · 2013: 10 · 2012: 3
- FWCI
- 1.47
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Bone (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Department of Veterans Affairs, Veterans Health Administration, Rehabilitation Research and Development Service (A4265R)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK067197)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone health and osteoporosis research
- Keywords
- calcitonin gene-related peptide, mesenchymal stem cells, osteogenic differentiation, osteoclastogenesis, bone resorption, RANKL, NF-κB activation, bone marrow-derived macrophages, CGRP receptor, sensory neuropeptides, bone mass regulation, capsaicin, cathepsin K, traps
- MeSH terms
- Alkaline Phosphatase, Animals, Bone Resorption, Cell Differentiation, Cells, Cultured, Male, Mice, Inbred C57BL, Microscopy, Fluorescence, Osteoclasts, Osteogenesis, Blotting, Western, Calcitonin Gene-Related Peptide, Polymerase Chain Reaction, NF-kappa B, Stromal Cells, Microscopy, Confocal, Cell Proliferation, Mice, RANK Ligand
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
