sFRP4-dependent Wnt signal modulation is critical for bone remodeling during postnatal development and age-related bone loss
Open accessAbstract
sFRP4 is an extracellular Wnt antagonist that fine-tunes its signal activity by direct binding to Wnts. Bone fragility under oxidative stress by diabetes and aging is partly related to the suppression of the Wnt signal through upregulated sFRP4. Here, to explore the functions of sFRP4 as a balancer molecule in bone development and remodeling, we analyzed the sFRP4 knock-in mouse strain. X-gal and immunohistochemically stained signals in sFRP4-LacZ heterozygous mice were detectable in restricted areas, mostly in osteoblasts and osteoclasts, of the femoral diaphysis after neonatal and postnatal stages. Histological and μCT analyses showed increased trabecular bone mass with alteration of the Wnt signal and osteogenic activity in sFRP4 mutants; this augmented the effect of the buildup of trabecular bone during the ageing period. Our results indicate that sFRP4 plays a critical role in bone development and remodeling by regulating osteoblasts and osteoclasts and that its functional loss prevents age-related bone loss in the trabecular bone area. These findings imply that sFRP4 functions as a key potential endogenous balancer of the Wnt signaling pathway by efficiently having direct influence on both bone formation and bone absorption during skeletal bone development and maintenance through remodeling.
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
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?
Mice lacking sFRP4 exhibit increased trabecular bone mass but reduced cortical bone thickness and failure of bone remodeling.
“Mice lacking sFRP4 exhibit increased trabecular bone mass but reduced cortical bone thickness and failure of bone remodeling (46).”
From Targeting myostatin/activin A protects against skeletal muscle and bone loss during spaceflight (2020) · cites this paper as [46]
The Results section, “Bone phenotypes of sFRP4-deficient mice,” reports increased trabecular bone mass and decreased cortical thickness in sFRP4-deficient mice. It does not report a failure of bone remodeling; the Discussion instead describes altered osteoblast and osteoclast activity that enhances bone deposition during remodeling. (LLM, conf=0.90)
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Guidelines for assessment of bone microstructure in rodents using micro–computed tomography
Bouxsein, M., Boyd, S. K., Christiansen, B., Guldberg, R. E., Jepsen, K. J., & Müller, R. (2010) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.141 · Cited by 4,461 · see citing works
Bone Resorption by Osteoclasts
Teitelbaum, S. L. (2000) · Science · doi:10.1126/science.289.5484.1504 · Cited by 3,962 · see citing works
LDL Receptor-Related Protein 5 (LRP5) Affects Bone Accrual and Eye Development
Gong, Y., Slee, R. B., Fukai, N., Rawadi, G., Roman-Roman, S., Reginato, A. M., Wang, H., Cundy, T., Glorieux, F. H., Lev, D., et al. (2001) · Cell · doi:10.1016/s0092-8674(01)00571-2 · Cited by 2,235 · see citing works
WNT signaling in bone homeostasis and disease: From human mutations to treatments
Baron, R., & Kneissel, M. (2013) · Nature Medicine · doi:10.1038/nm.3074 · Cited by 2,093 · see citing works
Jho, E., Zhang, T., Domon–Dell, C., Joo, C., Freund, J., & Costantini, F. D. (2002) · Molecular and Cellular Biology · doi:10.1128/mcb.22.4.1172-1183.2002 · Cited by 1,683 · see citing works
High Bone Density Due to a Mutation in LDL-Receptor–Related Protein 5
Boyden, L. M., Mao, J., Belsky, J., Mitzner, L., Farhi, A., Mitnick, M. A., Wu, D., Insogna, K., & Lifton, R. P. (2002) · New England Journal of Medicine · doi:10.1056/nejmoa013444 · Cited by 1,591 · see citing works
Secreted antagonists of the Wnt signalling pathway
Kawano, Y., & Kypta, R. (2003) · Journal of Cell Science · doi:10.1242/jcs.00623 · Cited by 1,584 · see citing works
Wnt Signaling: Multiple Pathways, Multiple Receptors, and Multiple Transcription Factors
Gordon, M. D., & Nusse, R. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.r600015200 · Cited by 1,333 · see citing works
Little, R. D., Folz, C., Manning, S. P., Swain, P. M., Zhao, S.-C., Eustace, B., Lappe, M. M., Spitzer, L., Zweier, S., Braunschweiger, K., et al. (2002) · The American Journal of Human Genetics · doi:10.1086/338450 · Cited by 1,282 · see citing works
Canonical WNT Signaling Promotes Osteogenesis by Directly Stimulating Runx2 Gene Expression
Gaur, T., Lengner, C. J., Hovhannisyan, H., Bhat, R. A., Bodine, P. V. N., Komm, B. S., Javed, A., van Wijnen, A. J., Stein, J. L., Stein, G. S., et al. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m500608200 · Cited by 1,170 · see citing works
The Osteoblast: A Sophisticated Fibroblast under Central Surveillance
Ducy, P. F., Schinke, T., & Karsenty, G. (2000) · Science · doi:10.1126/science.289.5484.1501 · Cited by 1,121 · see citing works
Estrogen Prevents Bone Loss via Estrogen Receptor α and Induction of Fas Ligand in Osteoclasts
Nakamura, T., Imai, Y., Matsumoto, T., Sato, S., Takeuchi, K., Igarashi, K., Harada, Y., Azuma, Y., Krust, A., Yamamoto, Y., et al. (2007) · Cell · doi:10.1016/j.cell.2007.07.025 · Cited by 1,013 · see citing works
Self-citationRegulation 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
BMP-2 Controls Alkaline Phosphatase Expression and Osteoblast Mineralization by a Wnt Autocrine Loop
Rawadi, G., Vayssière, B., Dunn, F. W., Baron, R., & Roman‐Roman, S. (2003) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.2003.18.10.1842 · Cited by 763 · see citing works
Yamaguchi, A., Komori, T., & Suda, T. (2000) · Endocrine Reviews · doi:10.1210/edrv.21.4.0403 · Cited by 688 · see citing works
Sequential roles of Hedgehog and Wnt signaling in osteoblast development
Hu, H., Hilton, M. J., Tu, X., Yu, K., Ornitz, D. M., & Long, F. (2005) · Development · doi:10.1242/dev.01564 · Cited by 682 · see citing works
Bovolenta, P., Esteve, P., Ruiz, J. M., Cisneros, E., & López-Rı́os, J. (2008) · Journal of Cell Science · doi:10.1242/jcs.026096 · Cited by 655 · see citing works
Genetic variability in adult bone density among inbred strains of mice
Beamer, W. G., Donahue, L. R., Rosen, C. J., & Baylink, D. J. (1996) · Bone · doi:10.1016/8756-3282(96)00047-6 · Cited by 630 · see citing works
Van Wesenbeeck, L., Cleiren, E., Gram, J., Beals, R. K., Bénichou, O., Scopelliti, D., Key, L., Renton, T., Bartels, C., Gong, Y., et al. (2003) · The American Journal of Human Genetics · doi:10.1086/368277 · Cited by 568 · see citing works
High Bone Mass in Mice Expressing a Mutant LRP5 Gene
Babij, P., Zhao, W., Small, C. G., Kharode, Y. P., Yaworsky, P. J., Bouxsein, M., Reddy, P. S., Bodine, P. V. N., Robinson, J. A., Bhat, B. M., et al. (2003) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.2003.18.6.960 · Cited by 497 · see citing works
Networks and hubs for the transcriptional control of osteoblastogenesis
Lian, J. B., Stein, G. S., Javed, A., van Wijnen, A. J., Stein, J. L., Montecino, M. A., Hassan, M. Q., Gaur, T., Lengner, C. J., & Young, D. W. (2006) · Reviews in Endocrine and Metabolic Disorders · doi:10.1007/s11154-006-9001-5 · Cited by 469 · see citing works
Bodine, P. V. N., Zhao, W., Kharode, Y. P., Bex, F. J., Lambert, A.-J., Goad, M. B., Gaur, T., Stein, G. S., Lian, J. B., & Komm, B. S. (2004) · Molecular Endocrinology · doi:10.1210/me.2003-0498 · Cited by 450 · 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
Osteoblast-derived WNT16 represses osteoclastogenesis and prevents cortical bone fragility fractures
Movérare‐Skrtic, S., Henning, P., Liu, X., Nagano, K., Saito, H., Börjesson, A., Sjögren, K., Windahl, S. H., Farman, H. H., Kindlund, B., et al. (2014) · Nature Medicine · doi:10.1038/nm.3654 · Cited by 364 · see citing works
Matsushita, M., Tsuboyama, T., Kasai, R., Okumura, H., Yamamuro, T., Higuchi, K., Higuchi, K., Kohno, A., Yonezu, T., & Utani, A. (1986) · PubMed Central · Cited by 233 · see citing works
Lee, H. X., Ambrosio, A. L., Reversade, B., & Robertis, E. M. D. (2006) · Cell · doi:10.1016/j.cell.2005.12.018 · Cited by 231 · see citing works
Leimeister, C., Bach, A., & Gessler, M. (1998) · Mechanisms of Development · doi:10.1016/s0925-4773(98)00072-0 · Cited by 222 · see citing works
Interaction between osteoblast and osteoclast: impact in bone disease.
Phan, T. C. A., Xu, J., & Zheng, M. (2004) · PubMed · doi:10.14670/hh-19.1325 · Cited by 207 · see citing works
In Vivo Analysis of Wnt Signaling in Bone
Glass, D. A., & Karsenty, G. (2007) · Endocrinology · doi:10.1210/en.2006-1372 · Cited by 200 · see citing works
Witte, F., Dokas, J., Neuendorf, F., Mundlos, S., & Stricker, S. (2009) · Gene Expression Patterns · doi:10.1016/j.gep.2008.12.009 · Cited by 199 · see citing works
Dominici, M., Rasini, V., Bussolari, R., Chen, X., Hofmann, T. J., Spano, C., Bernabei, D., Veronesi, E., Bertoni, F., Paolucci, P., et al. (2009) · Blood · doi:10.1182/blood-2008-10-183459 · Cited by 197 · see citing works
Canonical Wnt signaling inhibits osteoclastogenesis independent of osteoprotegerin
Albers, J., Keller, J., Baranowsky, A., Beil, F. T., Catalá-Lehnen, P., Schulze, J., Amling, M., & Schinke, T. (2013) · The Journal of Cell Biology · doi:10.1083/jcb.201207142 · Cited by 186 · see citing works
Vascular calcification is dependent on plasma levels of pyrophosphate
Lomashvili, K. A., Narisawa, S., Millán, J. L., & O'Neill, W. C. (2014) · Kidney International · doi:10.1038/ki.2013.521 · Cited by 161 · see citing works
WNT secretion and signalling in human disease
Herr, P., Hausmann, G., & Basler, K. (2012) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2012.06.008 · Cited by 158 · see citing works
Molecular analysis of coordinated bladder and urogenital organ formation by Hedgehog signaling
Haraguchi, R., Motoyama, J., Sasaki, H., Satoh, Y., Miyagawa, S., Nakagata, N., Moon, A., & Yamada, G. (2007) · Development · doi:10.1242/dev.02736 · Cited by 145 · see citing works
Self-citationLiu, Y., Strecker, S. E., Wang, L., Kronenberg, M. S., Wang, W., Rowe, D. W., & Maye, P. F. (2013) · PLoS ONE · doi:10.1371/journal.pone.0071318 · Cited by 143 · see citing works
Secreted Frizzled-Related Protein-1 Inhibits RANKL-Dependent Osteoclast Formation
Hausler, K. D., Horwood, N. J., Chuman, Y., Fisher, J., Ellis, J., Martin, T. J., Rubin, J. S., & Gillespie, M. T. (2004) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.040807 · Cited by 141 · see citing works
Osteoblast-Targeted Expression of Sfrp4 in Mice Results in Low Bone Mass
Nakanishi, R., Akiyama, H., Kimura, H. J., Otsuki, B., Shimizu, M., Tsuboyama, T., & Nakamura, T. (2007) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.071007 · Cited by 129 · see citing works
Estrogen receptor α in osteocytes regulates trabecular bone formation in female mice
Kondoh, S., Inoue, K., Igarashi, K., Sugizaki, H., Shirode-Fukuda, Y., Inoue, E., Yu, T., Takeuchi, J., Kanno, J., Bonewald, L. F., et al. (2013) · Bone · doi:10.1016/j.bone.2013.12.005 · Cited by 119 · see citing works
Self-citationQi, J. (2006) · World Journal of Gastroenterology · doi:10.3748/wjg.v12.i44.7113 · Cited by 110 · see citing works
Marsit, C. J., McClean, M. D., Furniss, C. S., & Kelsey, K. T. (2006) · International Journal of Cancer · doi:10.1002/ijc.22051 · Cited by 110 · see citing works
Signal transduction and transcriptional regulation during mesenchymal cell differentiation
Nishimura, R., Hata, K., Ikeda, F., Ichida, F., Shimoyama, A., Matsubara, T., Wada, M., Amano, K., & Yoneda, T. (2008) · Journal of Bone and Mineral Metabolism · doi:10.1007/s00774-007-0824-2 · Cited by 97 · see citing works
Secreted Frizzled-Related Protein 4 Is a Negative Regulator of Peak BMD in SAMP6 Mice
Nakanishi, R., Shimizu, M., Mori, M., Akiyama, H., Okudaira, S., Otsuki, B., Hashimoto, M., Higuchi, K., Hosokawa, M., Tsuboyama, T., et al. (2006) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.060719 · Cited by 97 · see citing works
Autocrine/Paracrine Secreted Frizzled-related Protein 2 Induces Cellular Resistance to Apoptosis
Lee, J.-L., Lin, C., Chueh, L.-L., & Chang, C. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m309008200 · Cited by 85 · see citing works
Characterization of Wnt/β‐catenin signalling in osteoclasts in multiple myeloma
Qiang, Y., Chen, Y., Brown, N., Hu, B., Epstein, J., Barlogie, B., & Shaughnessy, J. D. (2009) · British Journal of Haematology · doi:10.1111/j.1365-2141.2009.08009.x · Cited by 58 · see citing works
Tan, S. H., Senarath-Yapa, K., Chung, M. T., Longaker, M. T., Wu, J. Y., & Nusse, R. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1420463111 · Cited by 57 · see citing works
Belaya, Z. E., Rozhinskaya, L. Y., Mel'nichenko, G. A., Solodovnikov, A. G., Dragunova, N. V., Iljin, A. V., Dzeranova, L. K., & Dedov, I. I. (2013) · Osteoporosis International · doi:10.1007/s00198-013-2268-y · Cited by 45 · see citing works
Amano, K., Densmore, M., & Lanske, B. (2015) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.2582 · Cited by 40 · see citing works
Haraguchi, R., Matsumaru, D., Nakagata, N., Miyagawa, S., Suzuki, K., Kitazawa, S., & Yamada, G. (2012) · PLoS ONE · doi:10.1371/journal.pone.0042245 · Cited by 40 · see citing works
Self-citationCho, H. Y., Choi, H. J., Sun, H. J., Yang, J., An, J. H., Cho, S. W., Kim, S. W., Kim, S. Y., Kim, J. E., & Shin, C. S. (2010) · Bone · doi:10.1016/j.bone.2010.05.010 · Cited by 38 · see citing works
Loss of sfrp1 promotes ductal branching in the murine mammary gland
Gauger, K. J., Shimono, A., Crisi, G. M., & Schneider, S. S. (2012) · BMC Developmental Biology · doi:10.1186/1471-213x-12-25 · Cited by 36 · see citing works
Mori, K., Kitazawa, R., Kondo, T., Mori, M., Hamada, Y., Nishida, M., Minami, Y., Haraguchi, R., Takahashi, Y., & Kitazawa, S. (2014) · PLoS ONE · doi:10.1371/journal.pone.0102797 · Cited by 33 · see citing works
Self-citationGarufi, G., Seyhan, A. A., & Pasarica, M. (2014) · Obesity · doi:10.1002/oby.20915 · Cited by 26 · see citing works
Hikita, A., Iimura, T., Oshima, Y., Saitou, T., Yamamoto, S., & Imamura, T. (2015) · Bone · doi:10.1016/j.bone.2015.02.030 · Cited by 20 · see citing works
Epigenetic regulation of Tbx18 gene expression during endochondral bone formation
Haraguchi, R., Kitazawa, R., & Kitazawa, S. (2014) · Cell and Tissue Research · doi:10.1007/s00441-014-2028-0 · Cited by 19 · see citing works
Self-citationNakagawa, M., Kitazawa, R., Kuwahara, N., Yoshida, K., Haraguchi, R., & Kitazawa, S. (2013) · ACTA HISTOCHEMICA ET CYTOCHEMICA · doi:10.1267/ahc.12022 · Cited by 9 · see citing works
Self-citationBone disease drug discovery: examining the interactions between osteoblast and osteoclast
Sun, S. (2008) · Expert Opinion on Therapeutic Targets · doi:10.1517/14728222.12.2.239 · Cited by 9 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
The Regulation of Bone Metabolism and Disorders by Wnt Signaling
Maeda, K., Kobayashi, Y., Koide, M., Uehara, S., Okamoto, M., Ishihara, A., Kayama, T., Saito, M., & Marumo, K. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20225525 · Cited by 353 · see citing works
Vlashi, R., Zhang, X., Wu, M., & Chen, G. (2023) · Genes & Diseases · doi:10.1016/j.gendis.2022.07.011 · Cited by 165 · see citing works
Chesi, A., Wagley, Y., Johnson, M. E., Manduchi, E., Su, C., Lu, S., Leonard, M. E., Hodge, K. M., Pippin, J. A., Hankenson, K. D., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-09302-x · Cited by 158 · see citing works
Guo, L., Bertola, D. R., Takanohashi, A., Saito, A., Segawa, Y., Yokota, T., Ishibashi, S., Nishida, Y., Yamamoto, G. L., Franco, J. F. D. S., et al. (2019) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2019.03.004 · Cited by 133 · see citing works
WNT Signaling and Bone: Lessons From Skeletal Dysplasias and Disorders
Huybrechts, Y., Mortier, G. R., Boudin, E., & Hul, W. V. (2020) · Frontiers in Endocrinology · doi:10.3389/fendo.2020.00165 · Cited by 121 · see citing works
Targeting myostatin/activin A protects against skeletal muscle and bone loss during spaceflight
Lee, S.-J., Lehar, A., Meir, J. U., Koch, C., Morgan, A., Warren, L. E., Rydzik, R., Youngstrom, D. W., Chandok, H., George, J., et al. (2020) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2014716117 · Cited by 115 · see citing works
Cellular senescence in skeletal disease: mechanisms and treatment
He, X., Hu, W., Zhang, Y., Chen, M., Ding, Y., Yang, H., He, F., Gu, Q., & Shi, Q. (2023) · Cellular & Molecular Biology Letters · doi:10.1186/s11658-023-00501-5 · Cited by 96 · see citing works
Isojima, T., & Sims, N. A. (2021) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-021-03884-w · Cited by 78 · see citing works
WNT Signaling in Lung Aging and Disease
Lehmann, M., Baarsma, H. A., & Königshoff, M. (2016) · Annals of the American Thoracic Society · doi:10.1513/annalsats.201608-586aw · Cited by 70 · see citing works
Secreted frizzled related protein 4 (sFRP4) update: A brief review
Pawar, N. M., & Rao, P. (2018) · Cellular Signalling · doi:10.1016/j.cellsig.2018.01.019 · Cited by 72 · see citing works
Li, J., Bao, Q., Chen, S., Liu, H., Feng, J., Qin, H., Li, A., Liu, D., Shen, Y., Zhao, Y., et al. (2016) · Journal of Orthopaedic Research® · doi:10.1002/jor.23339 · Cited by 61 · see citing works
Preclinical Rodent Models for Human Bone Disease, Including a Focus on Cortical Bone
Koh, N. Y. Y., Miszkiewicz, J. J., Fac, M. L., Wee, N. K. Y., & Sims, N. A. (2024) · Endocrine Reviews · doi:10.1210/endrev/bnae004 · Cited by 60 · see citing works
Cheng, J., Gu, W., Lan, T., Deng, J., Ni, Z., Zhang, Z., Hu, Y., Sun, X., Yang, Y., & Xu, Q. (2020) · Cardiovascular Research · doi:10.1093/cvr/cvaa164 · Cited by 56 · see citing works
Chen, K., Ng, P. Y., Chen, R., Hu, D. Z., Berry, S., Baron, R., & Gori, F. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1900881116 · Cited by 45 · see citing works
Ueland, T., Stilgren, L. S., & Bollerslev, J. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20122896 · Cited by 37 · see citing works
Wnt Pathway Extracellular Components and Their Essential Roles in Bone Homeostasis
Martínez‐Gil, N., Ugartondo, N., Grinberg, D., & Balcells, S. (2022) · Genes · doi:10.3390/genes13010138 · Cited by 31 · see citing works
Kamizaki, K., Endo, M., Minami, Y., & Kobayashi, Y. (2020) · Developmental Dynamics · doi:10.1002/dvdy.151 · Cited by 32 · see citing works
The role of wnt signaling in diabetes-induced osteoporosis
Bao, K., Jiao, Y., Xing, L., Zhang, F., & Tian, F. (2023) · Diabetology & Metabolic Syndrome · doi:10.1186/s13098-023-01067-0 · Cited by 31 · see citing works
SFRP4 gene expression is increased in aggressive prostate cancer
Sandsmark, E., Andersen, M., Bofin, A. M., Bertilsson, H., Drabløs, F., Bathen, T. F., Rye, M. B., & Tessem, M. (2017) · Scientific Reports · doi:10.1038/s41598-017-14622-3 · Cited by 29 · see citing works
Azuma, K., Zhou, Q., & Kubo, K. (2018) · Medical Molecular Morphology · doi:10.1007/s00795-018-0188-9 · Cited by 28 · see citing works
The Wnt/β-catenin pathway is deregulated in cemento-ossifying fibromas
Pereira, T. D. S. F., Diniz, M. G., França, J. A., Moreira, R. G., de Menezes, G. H. F., de Sousa, S. F., Castro, W. H., Gomes, C. C., & Gomez, R. S. (2017) · Oral Surgery Oral Medicine Oral Pathology and Oral Radiology · doi:10.1016/j.oooo.2017.10.004 · Cited by 27 · see citing works
Boudin, E., & Hul, W. V. (2018) · Best Practice & Research Clinical Endocrinology & Metabolism · doi:10.1016/j.beem.2018.06.003 · Cited by 26 · see citing works
Mice lacking plastin-3 display a specific defect of cortical bone acquisition
Yorgan, T. A., Sari, H., Rolvien, T., Windhorst, S., Failla, A. V., Kornak, U., Oheim, R., Amling, M., & Schinke, T. (2019) · Bone · doi:10.1016/j.bone.2019.115062 · Cited by 26 · see citing works
Suthon, S., Lin, J., Perkins, R. S., Crockarell, J. R., Miranda‐Carboni, G. A., & Krum, S. A. (2021) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2021.11.018 · Cited by 25 · see citing works
Jiang, H., Liu, J., Chang, F., Wang, J., & Li, W. (2021) · International Journal of Molecular Medicine · doi:10.3892/ijmm.2021.4850 · Cited by 23 · see citing works
Translational studies provide insights for the etiology and treatment of cortical bone osteoporosis.
Brommage, R., & Ohlsson, C. (2018) · Best practice & research. Clinical endocrinology & metabolism · doi:10.1016/j.beem.2018.02.006 · Cited by 22 · see citing works
Haraguchi, R., Kitazawa, R., Imai, Y., & Kitazawa, S. (2018) · Histochemistry and Cell Biology · doi:10.1007/s00418-018-1641-5 · Cited by 21 · see citing works
Self-citationLuan, Y., Wu, S., Wang, M., Pu, Y., Zhao, Q., Ma, Y., Jiang, L., & He, X. (2023) · Biology · doi:10.3390/biology12040591 · Cited by 21 · see citing works
Yoon, H.-S., Kim, H. Y., Cho, K., Kim, Y., Woo, S., Kim, H. S., Kang, J.-L., Ryu, K., & Park, J. (2022) · Biology · doi:10.3390/biology11020255 · Cited by 19 · see citing works
A novel homozygous truncating mutation of the SFRP4 gene in Pyle's disease
Chatron, N., Lesca, G., Labalme, A., Rollat‐Farnier, P., Monin, P., Pichot, E., Edery, P., Sanlaville, D., & Rossi, M. (2017) · Clinical Genetics · doi:10.1111/cge.12907 · Cited by 19 · see citing works
Kaya, S., Schurman, C. A., Dole, N. S., Evans, D. S., & Alliston, T. N. (2020) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.4516 · Cited by 20 · see citing works
Altered Bone Status in Rett Syndrome
Pecorelli, A., Cordone, V., Schiavone, M. L., Caffarelli, C., Cervellati, C., Cerbone, G., Gonnelli, S., Hayek, J., & Valacchi, G. (2021) · Life · doi:10.3390/life11060521 · Cited by 18 · see citing works
Interference of miR-943-3p with secreted frizzled-related proteins4 (SFRP4) in an asthma mouse model
Shen, J. H., Zhao, J., Ye, Q.-Y., & Gu, X. (2019) · Cell and Tissue Research · doi:10.1007/s00441-019-03026-6 · Cited by 18 · see citing works
Sfrp4 and the Biology of Cortical Bone
Chen, R., Baron, R., & Gori, F. (2022) · Current Osteoporosis Reports · doi:10.1007/s11914-022-00727-w · Cited by 19 · see citing works
Osteoderms in a mammal the spiny mouse Acomys and the independent evolution of dermal armor
Maden, M., Polvadore, T., Polanco, A., Barbazuk, W. B., & Stanley, E. L. (2023) · iScience · doi:10.1016/j.isci.2023.106779 · Cited by 16 · see citing works
Roles of osteoclasts in pathological conditions
Kitazawa, S., Haraguchi, R., & Kitazawa, R. (2024) · Pathology International · doi:10.1111/pin.13500 · Cited by 15 · see citing works
Self-citationKim, H.-Y., Charton, C., Shim, J. H., Lim, S. Y., Kim, J.-H., Lee, S., Ohn, J. H., Kim, B., & Heo, C. Y. (2024) · Cells · doi:10.3390/cells13090729 · Cited by 16 · see citing works
Takaya, K., Asou, T., & Kishi, K. (2022) · Aging · doi:10.18632/aging.204273 · Cited by 15 · see citing works
Li, C., Liu, K., Dai, J., Li, X., Liu, X., Ni, W., Li, H., Wang, D., Qiao, J., Wang, Y., et al. (2021) · Gene · doi:10.1016/j.gene.2021.146020 · Cited by 14 · see citing works
Chen, Y., Zhang, Z., Jin, W., Li, Z., Bao, C., He, C., Guo, Y., & Li, C. (2022) · Animals · doi:10.3390/ani12070934 · Cited by 13 · see citing works
Mashhadikhan, M., Kheiri, H., & Dehghanifard, A. (2020) · Journal of Oral Biosciences · doi:10.1016/j.job.2020.08.001 · Cited by 11 · see citing works
Skeletal phenotypes and molecular mechanisms in aging mice
Guan, Q., 上海体育大学运动健康学院, 上. 2., Zhang, Y., Wang, Z., Liu, X.-H., Zou, J., & Zhang, L.-L. (2024) · 动物学研究 · doi:10.24272/j.issn.2095-8137.2023.397 · Cited by 11 · see citing works
Sowińska‐Seidler, A., Sztromwasser, P., Zawadzka, K., Sielski, D., Bukowska‐Olech, E., Zawadzki, P., Kozlowski, K. S., & Jamsheer, A. (2020) · Frontiers in Genetics · doi:10.3389/fgene.2020.593407 · Cited by 10 · see citing works
Developmental Contribution of Wnt-signal-responsive Cells to Mouse Reproductive Tract Formation
Haraguchi, R., Kitazawa, R., Murashima, A., Yamada, G., & Kitazawa, S. (2017) · ACTA HISTOCHEMICA ET CYTOCHEMICA · doi:10.1267/ahc.17017 · Cited by 9 · see citing works
Self-citationBrommage, R., Liu, J., & Powell, D. R. (2023) · Bone Research · doi:10.1038/s41413-022-00242-9 · Cited by 8 · see citing works
MicroCT analyses of mouse femoral neck architecture
Brommage, R., Jeter-Jones, S. L., Xiong, W., & Liu, J. (2019) · Bone · doi:10.1016/j.bone.2019.115040 · Cited by 8 · see citing works
Enfermedad de Pyle: un modelo humano de homeostasis corticotrabecular diferenciada
Arboleya, L. R., Queiró, R., Alpéri, M., Lorenzo, J. A., & Ballina, J. (2018) · Reumatología Clínica · doi:10.1016/j.reuma.2018.01.002 · Cited by 7 · see citing works
Xu, Y., Sun, J., Yang, X., Yu, Y., Mai, H., & Li, Z. (2017) · Journal of Oral and Maxillofacial Surgery · doi:10.1016/j.joms.2017.03.016 · Cited by 6 · see citing works
Ardura, J. A., Álvarez‐Carrión, L., Gortázar, A. R., & Alonso, V. (2020) · Elsevier eBooks · doi:10.1016/b978-0-12-818698-5.00006-7 · Cited by 7 · see citing works
Guo, Y., Cui, S., Xi, W., Wang, Y., Wu, B., Wang, Y., & Gu, Y. (2026) · Advanced Science · doi:10.1002/advs.202500046 · Cited by 5 · see citing works
Cord Blood Proteomic Profiles, Birth Weight, and Early Life Growth Trajectories
Pee, T. V., Martens, D. S., Alfano, R., Engelen, L., Sleurs, H., Rasking, L., Plusquin, M., & Nawrot, T. S. (2024) · JAMA Network Open · doi:10.1001/jamanetworkopen.2024.11246 · Cited by 5 · see citing works
Pyle's disease: A human model of differentiated cortical and trabecular homeostasis
Arboleya, L. R., Queiró, R., Alpéri, M., Lorenzo, J. A., & Ballina, J. (2019) · Reumatología Clínica (English Edition) · doi:10.1016/j.reumae.2018.01.005 · Cited by 5 · see citing works
Dikkopf-1 promotes matrix mineralization of osteoblasts by regulating Ca+-CAMK2A- CREB1 pathway
Park, H., Jo, S., Jang, M., Choi, S. H., & Kim, T. (2022) · BMB Reports · doi:10.5483/bmbrep.2022.55.12.103 · Cited by 4 · see citing works
Sex-specific nociceptor modulation of the apical periodontitis transcriptome
Lillis, K. V., Grinceviciute, R., & Diogenes, A. R. (2024) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2024.1338511 · Cited by 4 · see citing works
Girk3 deletion increases osteoblast maturation and bone mass accrual in adult male mice
Weaver, S. R., de Oliveira, H. T., Arnold, K. M., Zars, E. L., Peralta-Herrera, E., Taylor, E. L., Yu, K., de Velasco, E. M. F., Wickman, K. D., McGee‐Lawrence, M. E., et al. (2024) · JBMR Plus · doi:10.1093/jbmrpl/ziae108 · Cited by 4 · see citing works
WNT signaling in skeletal homeostasis and diseases
Gori, F., & Baron, R. (2020) · Elsevier eBooks · doi:10.1016/b978-0-12-813073-5.00012-5 · Cited by 4 · see citing works
Sawicki, S., Bugno‐Poniewierska, M., Żurowski, J., Szmatoła, T., Semik‐Gurgul, E., Bochenek, M., Karnas, E., & Gurgul, A. (2025) · Genes · doi:10.3390/genes16080936 · Cited by 3 · see citing works
Su, K., Cui, X., Zhou, J., Qiao, Y., & Liu, O. (2024) · Scientific Reports · doi:10.1038/s41598-024-76136-z · Cited by 3 · see citing works
Lee, S. M., Meyer, M. B., Benkusky, N. A., & Pike, J. W. (2023) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2023.106335 · Cited by 3 · see citing works
Dual role of Sfrp4 in bone remodelling during orthodontic tooth movement
Wang, Q., Wang, X., Chen, Y., & Pan, J. (2024) · Orthodontics and Craniofacial Research · doi:10.1111/ocr.12858 · Cited by 2 · see citing works
Fernandes, C. J. D. C. (2024) · Extracellular Vesicle · doi:10.1016/j.vesic.2024.100042 · Cited by 2 · see citing works
A review of thoracolumbar vertebrae number variation in sheep breeding
Yıldırır, M., Malmakov, N., Mussayeva, A., Оразымбетова, З., Бахтыбеккызы, Ш., Öner, Y., Bekitayeva, А. K., Omashev, K. B., & Арынгазиев, Б. (2024) · Small Ruminant Research · doi:10.1016/j.smallrumres.2024.107405 · Cited by 2 · see citing works
Haraguchi, R., Kitazawa, R., Kohara, Y., Imai, Y., & Kitazawa, S. (2022) · Cell and Tissue Research · doi:10.1007/s00441-022-03578-0 · Cited by 2 · see citing works
Self-citationChesi, A., Wagley, Y., Johnson, M. E., Manduchi, E., Su, C., Lu, S., Leonard, M. E., Hodge, K. M., Pippin, J. A., Hankenson, K. D., et al. (2018) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/405142 · Cited by 2 · see citing works
Systemic osteoprotegerin does not improve peri‐implant bone volume or osseointegration in rabbits
Choi, J. H., Wang, Z., Ross, F. P., van der Meulen, M. C. H., & Bostrom, M. P. (2020) · Journal of Orthopaedic Research® · doi:10.1002/jor.24884 · Cited by 1 · see citing works
Sfrp4 expression in thyroxine treated calvarial cells
Durham, E. L., Grey, Z. J., Black, L. E., Howie, R. N., Barth, J. L., Lee, B. S., & Cray, J. (2022) · Life Sciences · doi:10.1016/j.lfs.2022.121158 · Cited by 1 · see citing works
Hordyjewska‐Kowalczyk, E., Wuyts, W. A., Boeckx, N., Verdonck, A., Hendrickx, G., & Mortier, G. R. (2023) · Clinical Genetics · doi:10.1111/cge.14474 · Cited by 1 · see citing works
[Bisphosphonates-related osteonecrosis of the jaw: A case report].
Yang, J., Liu, Y., Qu, C., Sun, J., Li, T., & Shi, L. (2025) · PubMed Central · doi:10.19723/j.issn.1671-167x.2025.02.026 · Cited by 1 · see citing works
Recent Developments in Understanding the Role of Wnt Signaling in Skeletal Development and Disease
Zhong, Z. A., Ethen, N. J., & Williams, B. O. (2018) · Primer on the metabolic bone diseases and disorders of mineral metabolism · doi:10.1002/9781119266594.ch9
Maurizi, A., & Rucci, N. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-821666-8.00051-7
Tebben, P. J., & Kumar, R. (2020) · Elsevier eBooks · doi:10.1016/b978-0-12-813073-5.00010-1
Ohlsson, C. (2018) · Best Practice & Research Clinical Endocrinology & Metabolism · doi:10.1016/j.beem.2018.03.005
RetractedInsights into the evolution of dermal armour: osteoderms in a mammal, the spiny mouse, AcomysPreprint
Maden, M., Polvadore, T., Polanco, A., Barbazuk, W. B., & Stanley, E. L. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.10.17.512575
Impaired Wnt Signaling as a Cause of Skeletal Disorders
Yorgan, T. A., & Schinke, T. (2024) · Biology of extracellular matrix · doi:10.1007/978-3-031-70835-0_9
Lizcano, F., Avilés, E., López, C., Anaya, S. J. M., Ballesteros-García, M. C., Bustamante, L., Luna, F., Omeara, M., & Valenzuela, Á. (2026) · Frontiers in Endocrinology · doi:10.3389/fendo.2026.1870802
Cheng, Q., Shang, Y., Wang, H., & Han, M. (2026) · Turkish Journal of Biochemistry · doi:10.1515/tjb-2025-0277
Pyle disease – Functional validation of disease-causing missense variants in SFRP4/sFRP4
Magnus, L., Hordyjewska‐Kowalczyk, E., Sowińska‐Seidler, A., Ryhänen, E., Jamsheer, A., Mortier, G. R., Mäkitie, O., & Hendrickx, G. (2026) · Bone · doi:10.1016/j.bone.2026.118037
- Authors
- Haraguchi, R., Kitazawa, R., Mori, K., Tachibana, R., Kiyonari, H., Imai, Y., Abe, T., & Kitazawa, S.
- Affiliations
- Ehime University (JP)
- Ehime University Hospital (JP)
- Osaka National Hospital (JP)
- RIKEN (JP)
- Corresponding author
- Kitazawa, Sohei
- ORCID
- Venue
- Scientific Reports
- Published
- 2016-04-27
- Volume
- 6
- Issue
- 1
- Pages
- 25198-25198
- ISSN
- 2045-2322 (ISSN-L)
- PMC
- PMC4846872
- OpenAlex
- W2342999456
- Cited by
- 77
- References
- 57
- Citations by year
- 2026: 4 · 2025: 2 · 2024: 12 · 2023: 7 · 2022: 10 · 2021: 6 · 2020: 11 · 2019: 9 · 2018: 9 · 2017: 5 · 2016: 2
- FWCI
- 4.33
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Scientific Reports (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Ministry of Education, Culture, Sports, Science and Technology (15K08426)
- Japan Society for the Promotion of Science (15K08426, 15H04961, 16H05161, 15K08136, 15K15552, 26670176)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Wnt/β-catenin signaling in development and cancer
- Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone health and osteoporosis research
- Keywords
- SFRP4, Wnt signaling, bone remodeling, postnatal bone development, age-related bone loss, osteoblasts, osteoclasts, trabecular bone mass, bone fragility, oxidative stress, diabetes mellitus, bone formation and resorption
- MeSH terms
- Cancellous Bone, Secreted Frizzled-Related Proteins, Animals, Disease Models, Animal, Osteoblasts, Osteoclasts, Osteoporosis, Proto-Oncogene Proteins, Bone Remodeling, Mice, Gene Knock-In Techniques, Wnt Signaling Pathway
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
