RANKL, Ephrin-Eph and Wnt10b are key intercellular communication molecules regulating bone remodeling in autologous transplanted goldfish scales
Abstract
This study aimed to investigate the precise data of gene expression, functions, and chronological relationships amongst communication molecules involved in the bone remodeling process with an in vivo model using autologous transplanted scales of goldfish. Autotransplantation of methanol-fixed cell-free scales triggers scale resorption and regeneration, as well as helps elucidate the process of bone remodeling. We investigated osteoclastic markers, osteoblastic markers, and gene expressions of communicating molecules (RANKL, ephrinB2, EphB4, EphA4, Wnt10b) by qPCR, in situ hybridization for Wnt10b, and immunohistochemistry for EphrinB2 and EphA4 proteins to elucidate the bone remodeling process. Furthermore, functional inhibition experiments for the signaling of ephrinB2/Eph, ephrin/EphA4, and Wnt10b using specific antibodies, revealed that these proteins are involved in key signaling pathways promoting normal bone remodeling. Our data suggests that the remodeling process comprises of two successive phases. In the first absorption phase, differentiation of osteoclast progenitors by RANKL is followed by the bone absorption by mature, active osteoclasts, with the simultaneous induction of osteoblast progenitors by multinucleated osteoclast-derived Wnt10b, and proliferation of osteoblast precursors by ehprinB2/EphB4 signaling. Subsequently, during the second formation phase, termination of bone resorption by synergistic cooperation occurs, with downregulation of RANKL expression in activated osteoblasts and Ephrin/EphA4-mediated mutual inhibition between neighboring multinucleated osteoclasts, along with simultaneous activation of osteoblasts via forward and reverse EphrinB2/EphB4 signaling between neighboring osteoblasts. In addition, the present study shows that autologous transplantation of methanol-fixed cell-free scale is an ideal in vivo model to study bone remodeling.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
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?
EphrinB2-EphB4 bidirectional signaling must function locally and requires direct cell-cell contact since both receptors are anchored to the cell membrane, as shown with a goldfish scale model of bone remodeling.
“EphrinB2–EphB4 bidirectional signaling must function locally and requires direct cell‐cell contact since both receptors are anchored to the cell membrane, as shown with goldfish scale model of bone remodeling.252”
From Bone remodeling: an operational process ensuring survival and bone mechanical competence (2022) · cites this paper as [252]
Cites
Suda, T., Takahashi, N., Udagawa, N., Jimi, E., Gillespie, M. T., & Martin, T. J. (1999) · Endocrine Reviews · doi:10.1210/edrv.20.3.0367 · Cited by 2,317 · see citing works
Schaeren‐Wiemers, N., & Gerfin-Moser, A. (1993) · Histochemistry and Cell Biology · doi:10.1007/bf00267823 · Cited by 1,162 · see citing works
Eph receptor signalling casts a wide net on cell behaviour
Pasquale, E. B. (2005) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1662 · Cited by 1,013 · see citing works
Regulation of osteoblastogenesis and bone mass by Wnt10b
Bennett, C. N., Longo, K. A., Hahn, W. S., Suva, L. J., Lane, T. F., Hankenson, K. D., & MacDougald, O. A. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0408742102 · Cited by 882 · see citing works
Gale, N. W., Holland, S. J., Valenzuela, D. M., Flenniken, A. M., Pan, L., Ryan, T. E., Henkemeyer, M. J., Strebhardt, K., Hirai, H., Wilkinson, D. G., et al. (1996) · Neuron · doi:10.1016/s0896-6273(00)80276-7 · Cited by 839 · see citing works
Bidirectional ephrinB2-EphB4 signaling controls bone homeostasis
Zhao, C., Irie, N., Takada, Y., Shimoda, K., Miyamoto, T., Nishiwaki, T., Suda, T., & Matsuo, K. (2006) · Cell Metabolism · doi:10.1016/j.cmet.2006.05.012 · Cited by 777 · see citing works
A two-color acid-free cartilage and bone stain for zebrafish larvae
Walker, M., & Kimmel, C. (2007) · Biotechnic & Histochemistry · doi:10.1080/10520290701333558 · Cited by 730 · see citing works
Sims, N. A., & Martin, T. J. (2014) · BoneKEy Reports · doi:10.1038/bonekey.2013.215 · Cited by 706 · see citing works
Pederson, L., Ruan, M., Westendorf, J. J., Khosla, S., & Oursler, M. J. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0805133106 · Cited by 556 · see citing works
Suppression of bone formation by osteoclastic expression of semaphorin 4D
Negishi-Koga, T., Shinohara, M., Komatsu, N., Bito, H., Kodama, T., Friedel, R. H., & Takayanagi, H. (2011) · Nature Medicine · doi:10.1038/nm.2489 · Cited by 498 · see citing works
Repelling class discrimination: ephrin-A5 binds to and activates EphB2 receptor signaling
Himanen, J., Chumley, M. J., Lackmann, M., Li, C., Barton, W. A., Jeffrey, P. D., Vearing, C., Geleick, D., Feldheim, D. A., Boyd, A., et al. (2004) · Nature Neuroscience · doi:10.1038/nn1237 · Cited by 453 · see citing works
Mizoguchi, T., Pinho, S., Ahmed, J. U., Kunisaki, Y., Hanoun, M., Mendelson, A., Ono, N., Kronenberg, H. M., & Frenette, P. S. (2014) · Developmental Cell · doi:10.1016/j.devcel.2014.03.013 · Cited by 441 · see citing works
Wnt10b Increases Postnatal Bone Formation by Enhancing Osteoblast Differentiation
Bennett, C. N., Ouyang, H., Li, Y., Zeng, Q., Gerin, I., Sousa, K. M., Lane, T. F., Krishnan, V., Hankenson, K. D., & MacDougald, O. A. (2007) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.070810 · Cited by 282 · see citing works
Cole, A. A., & Walters, L. M. (1987) · Journal of Histochemistry & Cytochemistry · doi:10.1177/35.2.3540104 · Cited by 195 · see citing works
Regeneration of teleost fish scale
Bereiter‐Hahn, J., & Zylberberg, L. (1993) · Comparative Biochemistry and Physiology Part A Physiology · doi:10.1016/0300-9629(93)90262-3 · Cited by 187 · see citing works
Irie, N., Takada, Y., Watanabe, Y., Matsuzaki, Y., Naruse, C., Asano, M., Iwakura, Y., Suda, T., & Matsuo, K. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m807598200 · Cited by 175 · see citing works
Bone cell interactions through Eph/ephrin: Bone modeling, remodeling and associated diseases
Matsuo, K., & Otaki, N. (2012) · Cell Adhesion & Migration · doi:10.4161/cam.20888 · Cited by 167 · see citing works
Roles of Wnt signalling in bone growth, remodelling, skeletal disorders and fracture repair
Macsai, C. E., Foster, B. K., & Xian, C. J. (2008) · Journal of Cellular Physiology · doi:10.1002/jcp.21342 · Cited by 152 · see citing works
Eph Receptors and Ephrin Signaling Pathways: A Role in Bone Homeostasis
Edwards, C. M., & Mundy, G. R. (2008) · International Journal of Medical Sciences · doi:10.7150/ijms.5.263 · Cited by 121 · see citing works
CLONING AND CHARACTERIZATION OF OSTEOCLAST PRECURSORS FROM THE RAW264.7 CELL LINE
Cuetara, B., Crotti, T. N., O’Donoghue, A. J., & McHugh, K. P. (2006) · In Vitro Cellular & Developmental Biology - Animal · doi:10.1290/0510075.1 · Cited by 86 · see citing works
Immature osteoblast lineage cells increase osteoclastogenesis in osteogenesis imperfecta murine.
Li, H., Jiang, X., Delaney, J., Franceschetti, T., Bilić-Ćurčić, I., Kalinovsky, J., Lorenzo, J., Grčević, D., Rowe, D., & Kalajzić, I. (2010) · American Journal of Pathology · doi:10.2353/ajpath.2010.090704 · Cited by 65 · see citing works
Ephrin B2/EphB4 Mediates the Actions of IGF-I Signaling in Regulating Endochondral Bone Formation
Wang, Y., Menendez, A., Fong, C., Elalieh, H. Z., Chang, W., & Bikle, D. D. (2014) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.2196 · Cited by 53 · see citing works
Reduced osteoblastic population and defective mineralization in osteopetrotic (op/op) mice
Sakagami, N., Amizuka, N., Li, M., Takeuchi, K., Hoshino, M., Nakamura, M., Nozawa‐Inoue, K., Udagawa, N., & Maeda, T. (2005) · Micron · doi:10.1016/j.micron.2005.06.008 · Cited by 51 · see citing works
Thamamongood, T. A., Furuya, R., Fukuba, S., Nakamura, M., Suzuki, N., & Hattori, A. (2012) · Bone · doi:10.1016/j.bone.2012.03.021 · Cited by 47 · see citing works
Self-citationKitamura, K., Takahira, K., Inari, M., Satoh, Y., Hayakawa, K., Tabuchi, Y., Ogai, K., Nishiuchi, T., Kondo, T., Mikuni‐Takagaki, Y., et al. (2013) · Comparative Biochemistry and Physiology Part A Molecular & Integrative Physiology · doi:10.1016/j.cbpa.2013.04.023 · Cited by 41 · see citing works
Self-citationEphA4 Receptor Is a Novel Negative Regulator of Osteoclast Activity
Stiffel, V. M., Amoui, M., Sheng, M. H. ‐., Mohan, S., & Lau, K. ‐. W. (2013) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.2084 · Cited by 36 · see citing works
Significance of the fibrous stroma in bone invasion by human gingival squamous cell carcinomas
Ishikuro, M., Sakamoto, K., Kayamori, K., Akashi, T., Kanda, H., Izumo, T., & Yamaguchi, A. (2008) · Bone · doi:10.1016/j.bone.2008.05.014 · Cited by 35 · see citing works
Hamazaki, K., Suzuki, N., Kitamura, K., et al. (2016) · Prostaglandins Leukotrienes and Essential Fatty Acids · doi:10.1016/j.plefa.2016.04.001 · Cited by 34 · see citing works
Self-citationSato, K., Lee, J., Sakamoto, K., et al. (2013) · American Journal Of Pathology · doi:10.1016/j.ajpath.2013.01.038 · Cited by 29 · see citing works
Ogai, K., Hisano, S., Mawatari, K., et al. (2012) · Neurochemistry International · doi:10.1016/j.neuint.2012.08.015 · Cited by 22 · see citing works
Self-citationEffects of hyperglycemia on bone metabolism and bone matrix in goldfish scales
Kitamura, K.-I., Andoh, T., Okesaku, W., et al. (2016) · Comparative Biochemistry and Physiology Part A Molecular & Integrative Physiology · doi:10.1016/j.cbpa.2016.09.010 · Cited by 10 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Bone remodeling: an operational process ensuring survival and bone mechanical competence
Bolamperti, S., Villa, I., & Rubinacci, A. (2022) · Bone Research · doi:10.1038/s41413-022-00219-8 · Cited by 482 · see citing works
- Authors
- Tazaki, Y., Sugitani, K., Ogai, K., Kobayashi, I., Kawasaki, H., Aoyama, T., Suzuki, N., Tabuchi, Y., Hattori, A., & Kitamura, K.-I.
- Affiliations
- Kanazawa University (JP)
- University of Toyama (JP)
- Tokyo Medical and Dental University (JP)
- Corresponding author
- Kitamura, Kei-ichiro
- Venue
- Comparative Biochemistry and Physiology Part A: Molecular & Integrative Physiology
- Publisher
- Elsevier BV
- Published
- 2018-11
- Volume
- 225
- Pages
- 46-58
- ISSN
- 1095-6433 (ISSN-L)
- OpenAlex
- W2808520997
- Cited by
- 15
- References
- 31
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 2 · 2023: 2 · 2022: 3 · 2021: 3 · 2020: 3
- FWCI
- 0.53
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Comparative Biochemistry and Physiology Part A Molecular & Integrative Physiology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- JSPS (15K01705, 17K01353, 16K07871)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Medicinal Plant Pharmacodynamics Research
- Keywords
- bone remodeling, autologous transplantation, RANKL, EphA4, Wnt10b, osteoclasts, osteoblasts, bone resorption, bone regeneration, intercellular communication
- MeSH terms
- Animal Scales, Animals, Cell Communication, Goldfish, Osteoblasts, Osteoclasts, Blotting, Western, Bone Remodeling, Fish Proteins, Ephrins, Wnt Proteins, 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
