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Cortical-Bone Fragility — Insights from sFRP4 Deficiency in Pyle’s Disease
Open accessAbstract
BACKGROUND: Cortical-bone fragility is a common feature in osteoporosis that is linked to nonvertebral fractures. Regulation of cortical-bone homeostasis has proved elusive. The study of genetic disorders of the skeleton can yield insights that fuel experimental therapeutic approaches to the treatment of rare disorders and common skeletal ailments. METHODS: We evaluated four patients with Pyle's disease, a genetic disorder that is characterized by cortical-bone thinning, limb deformity, and fractures; two patients were examined by means of exome sequencing, and two were examined by means of Sanger sequencing. After a candidate gene was identified, we generated a knockout mouse model that manifested the phenotype and studied the mechanisms responsible for altered bone architecture. RESULTS: In all affected patients, we found biallelic truncating mutations in SFRP4, the gene encoding secreted frizzled-related protein 4, a soluble Wnt inhibitor. Mice deficient in Sfrp4, like persons with Pyle's disease, have increased amounts of trabecular bone and unusually thin cortical bone, as a result of differential regulation of Wnt and bone morphogenetic protein (BMP) signaling in these two bone compartments. Treatment of Sfrp4-deficient mice with a soluble Bmp2 receptor (RAP-661) or with antibodies to sclerostin corrected the cortical-bone defect. CONCLUSIONS: Our study showed that Pyle's disease was caused by a deficiency of sFRP4, that cortical-bone and trabecular-bone homeostasis were governed by different mechanisms, and that sFRP4-mediated cross-regulation between Wnt and BMP signaling was critical for achieving proper cortical-bone thickness and stability. (Funded by the Swiss National Foundation and the National Institutes of Health.).
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“sFRP4 is known to be a Wnt regulator, and mutations in SFRP4 in humans have been shown to cause Pyle disease, which is characterized by cortical bone fragility and fractures (45).”
From Targeting myostatin/activin A protects against skeletal muscle and bone loss during spaceflight (2020) · cites this paper as [45]
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Cites
Analysis of Relative Gene Expression Data Using Real-Time Quantitative PCR and the 2−ΔΔCT Method
Livak, K. J., & Schmittgen, T. D. (2001) · Methods · doi:10.1006/meth.2001.1262 · Cited by 180,860 · cited 1×
“In Panels E, F, and G, fold differences in mRNA expression relative to that in wild-type cells were calculated as described by Livak and Schmittgen.(18) Panel H shows the effects of Sfrp4 deletion on Smad1, Smad5,”
MethodMutation of the mouse klotho gene leads to a syndrome resembling ageing
Kuro-o, M., Matsumura, Y., Aizawa, H., Kawaguchi, H., Suga, T., Utsugi, T., Ohyama, Y., Kurabayashi, M., Kaname, T., Kume, E., et al. (1997) · Nature · doi:10.1038/36285 · Cited by 3,837
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
Self-citationBlack, D. M., & Rosen, C. J. (2016) · New England Journal of Medicine · doi:10.1056/nejmcp1513724 · Cited by 1,790
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
Canonical wnt signaling in differentiated osteoblasts controls osteoclast differentiation.
Glass, D. A., Bialek, P., Ahn, J. D., Starbuck, M., Patel, M. S., Clevers, H., Taketo, M. M., Long, F., McMahon, A. P., Lang, R. A., et al. (2005) · Developmental Cell · doi:10.1016/j.devcel.2005.02.017 · Cited by 1,558
Increased bone density in sclerosteosis is due to the deficiency of a novel secreted protein (SOST)
Balemans, W. (2001) · Human Molecular Genetics · doi:10.1093/hmg/10.5.537 · Cited by 1,147
Cho, Y. S., Go, M. J., Kim, Y. J., Heo, J. Y., Oh, J. H., Ban, H., Yoon, D., Lee, M. H., Kim, D. J., Park, M., et al. (2009) · Nature Genetics · doi:10.1038/ng.357 · Cited by 1,017
Sclerostin is a delayed secreted product of osteocytes that inhibits bone formation
Poole, K. E. S., Van Bezooijen, R. L., Loveridge, N., Hamersma, H., Papapoulos, S. E., Löwik, C. W., & Reeve, J. (2005) · The FASEB Journal · doi:10.1096/fj.05-4221fje · Cited by 965
van Bezooijen, R. L., Roelen, B. A. J., Visser, A., van der Wee-Pals, L. J. A., de Wilt, E., Karperien, M., Hamersma, H. A., Papapoulos, S. E., ten Dijke, P., & Löwik, C. W. G. M. (2004) · The Journal of Experimental Medicine · doi:10.1084/jem.20031454 · Cited by 893
Research works printed but not linked: 2
- Cohn M, 1933, Fortschr Röntgenstr, 47, 293
- Pyle E, 1931, J Bone Joint Surg Am, 13, 874
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Liu, J., Xiao, Q., Xiao, J., Niu, C., Li, Y., Zhang, X., Zhou, Z., Shu, G., & Yin, G. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-021-00762-6 · Cited by 2,519
“Cortical bone determines bone strength; thus, cortical bone fragility is also a susceptibility factor for fractures.(140,141) Inflammation plays an important role in tissue regeneration and bone loss.”
BackgroundSelf-citationThe 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 360
“1) Loss-of-function (AR) Pyle disease metaphyseal dysplasia 265900 wide trabecular metaphyses, thin cortical bone, bone fragility [33]”
BackgroundMolecular genetics and targeted therapy of WNT-related human diseases (Review)
Katoh, M., & Katoh, M. (2017) · International Journal of Molecular Medicine · doi:10.3892/ijmm.2017.3071 · Cited by 216
“Heterozygous loss-of-function mutation in the LRP6 gene (R611C) was found in patients with familial osteoporosis and early-onset coronary artery disease (75).”
BackgroundVlashi, R., Zhang, X., Wu, M., & Chen, G. (2023) · Genes & Diseases · doi:10.1016/j.gendis.2022.07.011 · Cited by 165
“Gene alterations in SFRP4 are known to cause bone disorders such as metaphyseal chondrodysplasia (also known as the Pyle’s disease), characterized flaring of the ends of long bones amongst other abnormalities.(188) Upraised SFRP4 levels are linked to osteomalacia, characterized by a soft andmore flexible bone.”
BackgroundJansson, P., Curiac, D., Ahrén, I. L., Hansson, F., Niskanen, T. M., Sjögren, K., & Ohlsson, C. (2019) · The Lancet Rheumatology · doi:10.1016/s2665-9913(19)30068-2 · Cited by 168
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
Toward a Consensus View of Mammalian Adipocyte Stem and Progenitor Cell Heterogeneity.
Ferrero, R., Rainer, P., & Deplancke, B. (2020) · Trends in Cell Biology · doi:10.1016/j.tcb.2020.09.007 · Cited by 114
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
Self-citationWNT 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 123
“Since 2016, various biallelic truncating mutations in sFRP4 have been confirmed to cause Pyle disease (70, 72, 73).”
BackgroundWu, X., Que, H., Li, Q., & Wei, X. (2025) · Molecular Cancer · doi:10.1186/s12943-025-02363-1 · Cited by 155
“…addition, dysregulated Wnt/β-catenin signaling contributes to pathological processes in other organ systems, including cortical bone fragility in osteoporosis [41], neuronal mitochondrial dysfunction in neurodegenerative diseases [42], and liver regeneration in hepatocellular carcinoma (HCC) [43].”
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Mäkitie, R. E., Costantini, A., Kämpe, A., Alm, J. J., & Mäkitie, O. (2019) · Frontiers in Endocrinology · doi:10.3389/fendo.2019.00070 · Cited by 108
“Correspondingly, Sfrp4-null mice present with increased trabecular bone, decreased cortical bone and failure in bone modeling (65).”
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Lerner, U. H., Kindstedt, E., & Lundberg, P. (2019) · Journal Of Clinical Periodontology · doi:10.1111/jcpe.13051 · Cited by 100
Sclerostin neutralization unleashes the osteoanabolic effects of Dkk1 inhibition
Witcher, P. C., Miner, S. E., Horan, D. J., Bullock, W. A., Lim, K., Kang, K. S., Adaniya, A. L., Ross, R. D., Loots, G. G., & Robling, A. G. (2018) · JCI Insight · doi:10.1172/jci.insight.98673 · Cited by 93
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Li, S., He, S., Xie, P.-Y., Li, W., Zhang, X., Li, T.-F., & Li, D. (2021) · Frontiers in Pharmacology · doi:10.3389/fphar.2021.717065 · Cited by 91
Roles of Non-Canonical Wnt Signalling Pathways in Bone Biology
Lojk, J., & Marc, J. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms221910840 · Cited by 88
Transferrin receptor 2 controls bone mass and pathological bone formation via BMP and Wnt signalling
Rauner, M., Baschant, U., Roetto, A., Pellegrino, R. M., Rother, S., Salbach-Hirsch, J., Weidner, H., Hintze, V., Campbell, G., Petzold, A., et al. (2019) · Nature Metabolism · doi:10.1038/s42255-018-0005-8 · Cited by 87
Isojima, T., & Sims, N. A. (2021) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-021-03884-w · Cited by 86
NOTUM inhibition increases endocortical bone formation and bone strength
Brommage, R., Liu, J., Vogel, P., Mseeh, F., Thompson, A. Y., Potter, D., Shadoan, M. K., Hansen, G. M., Jeter-Jones, S. L., Cui, J., et al. (2019) · Bone Research · doi:10.1038/s41413-018-0038-3 · Cited by 75
Self-citationWnt signaling in bone, kidney, intestine, and adipose tissue and interorgan interaction in aging
Chen, D., Xie, R., Shu, B., LANDAY, A. L., Wei, C., Reiser, J., Spagnoli, A., Torquati, A., Forsyth, C. B., Keshavarzian, A., et al. (2018) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.13945 · Cited by 69
Holdsworth, G., Greenslade, K. J., Jose, J., Stencel, Z., Kirby, H., Moore, A., Ke, H. Z., & Robinson, M. K. (2017) · Bone · doi:10.1016/j.bone.2017.11.003 · Cited by 65
CircRUNX2 through has‐miR‐203 regulates RUNX2 to prevent osteoporosis
Yin, Q., Wang, J., Fu, Q., Gu, S., & Rui, Y. (2018) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.13888 · Cited by 60
“It is a skeletal disease characterized by low bone mass, defective bone structure, and high risks of fracture even under minor pressure.(2) In the world, about 200 million people suffered from the osteoporosis, and the insufferable pain and possible complications of which affect the life quality of patients greatly.”
BackgroundPreclinical 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 67
Wang, F., Tarkkonen, K. M., Nieminen-Pihala, V., Nagano, K., Majidi, R. A., Puolakkainen, T., Rummukainen, P., Lehto, J., Roivainen, A., Zhang, F., et al. (2019) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.3680 · Cited by 51
“These data show that the role of Wnt1 in regulating bone metabolism is distinct from many other components of the Wnt signaling pathway, as for example the deletion of Wnt16 leads to decreased cortical bone mass and deletion of Wnt10b to decreased trabecular bone mass, osteoblast-targeted Wnt5a knockouts exhibit low t…”
BackgroundSelf-citationColditz, J., Thiele, S., Baschant, U., Niehrs, C., Bonewald, L. F., Hofbauer, L. C., & Rauner, M. (2018) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.3463 · Cited by 47
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BackgroundResultChen, 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
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Secreted Frizzled Related Proteins in Cardiovascular and Metabolic Diseases
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Koike, Y., Takahata, M., Nakajima, M., Otomo, N., Suetsugu, H., Liu, X., Endo, T., Imagama, S., Kobayashi, K., Kaito, T., et al. (2023) · eLife · doi:10.7554/elife.86514 · Cited by 42
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Boudin, E., & Hul, W. V. (2017) · European Journal of Endocrinology · doi:10.1530/eje-16-0990 · Cited by 42
Claudel, M., Jouzeau, J., & Cailotto, F. (2019) · FEBS Journal · doi:10.1111/febs.15119 · Cited by 39
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Guo, L. Z., & Ikegawa, S. (2021) · Journal of Human Genetics · doi:10.1038/s10038-021-00942-w · Cited by 35
Nfonsam, L. E., Jandová, J., Jecius, H., Omesiete, P. N., & Nfonsam, V. N. (2019) · World Journal of Gastrointestinal Oncology · doi:10.4251/wjgo.v11.i8.589 · Cited by 35
Nie, X., Xia, F., Liu, Y., Zhou, Y., Ye, W., Hean, P., Meng, J., Liu, H., Liu, L., Wen, J.-X., et al. (2019) · Frontiers in Pharmacology · doi:10.3389/fphar.2019.01110 · Cited by 34
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BackgroundChen, K., Chen, X., Lang, C., Yuan, X., Huang, J., Li, Z., Xu, M., Wu, K., Zhou, C., Li, Q., et al. (2023) · Experimental & Molecular Medicine · doi:10.1038/s12276-023-01085-y · Cited by 32
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Hannan, F. M., Newey, P. J., Whyte, M. P., & Thakker, R. V. (2018) · British Journal of Clinical Pharmacology · doi:10.1111/bcp.13803 · Cited by 32
Movérare‐Skrtic, S., Nilsson, K. H., Henning, P., Funck‐Brentano, T., Nethander, M., Rivadeneira, F., Nunes, G. C., Koskela, A., Tuukkanen, J., Tuckermann, J. P., et al. (2019) · The FASEB Journal · doi:10.1096/fj.201900707r · Cited by 32
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Kamizaki, K., Endo, M., Minami, Y., & Kobayashi, Y. (2020) · Developmental Dynamics · doi:10.1002/dvdy.151 · Cited by 36
“A possible mechanism by which Sfrp4 regulates cortical thickness is proposed as follows: Wnt5a increases the expression of BMP2, which in turn promotes the expression of canonical Wnt inhibitor sclerostin.(92) Increased sclerostin expression suppresses bone accrual in cortical bone.”
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“The loss of canonical Wnt signaling pathway inhibition in SFRP4-KO mice caused increases in bone trabecular bone mass [92].”
BackgroundHe, G., Shi, Y., Lim, J., Bellido, T., Ni, J., & Long, F. (2017) · Bone Research · doi:10.1038/boneres.2017.16 · Cited by 31
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Galada, C., Shah, H. H., Shukla, A., & Girisha, K. M. (2017) · Journal of Human Genetics · doi:10.1038/jhg.2016.166 · Cited by 29
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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
Azuma, K., Zhou, Q., & Kubo, K. (2018) · Medical Molecular Morphology · doi:10.1007/s00795-018-0188-9 · Cited by 28
“Treatment with a Bmp2 receptor or antibody to sclerostin correlated the cortical bone defect [56].”
BackgroundInfluentialMechanistic insights into skeletal development gained from genetic disorders
Yip, R. K. H., Chan, D. T.-M., & Cheah, K. S. E. (2019) · Current topics in developmental biology/Current Topics in Developmental Biology · doi:10.1016/bs.ctdb.2019.02.002 · Cited by 26
Guo, L. Z., Iida, A., Bhavani, G. S., Gowrishankar, K., Wang, Z., Xue, J.-Y., Wang, J., Miyake, N., Matsumoto, N., Hasegawa, T., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-22340-8 · Cited by 27
“The study was approved by the ethical committee of RIKEN, Kasturba Hospital, Manipal, and participating institutions (approval number: 17-16-40(3)).”
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Gori, F., Superti‐Furga, A., & Baron, R. (2016) · New England Journal of Medicine · doi:10.1056/nejmc1609768 · Cited by 27
Self-citationBoudin, E., & Hul, W. V. (2018) · Best Practice & Research Clinical Endocrinology & Metabolism · doi:10.1016/j.beem.2018.06.003 · Cited by 29
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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
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Handa, A., Nishimura, G., Zhan, M. X., Bennett, D. L., & El-Khoury, G. Y. (2021) · Japanese Journal of Radiology · doi:10.1007/s11604-021-01206-5 · Cited by 25
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Ohlsson, C., Nilsson, K. H., Henning, P., Wu, J., Gustafsson, K. L., POUTANEN, M. H., Lerner, U. H., & Movérare‐Skrtic, S. (2018) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00292.2017 · Cited by 25
Brommage, R., Powell, D. R., & Vogel, P. (2019) · Disease Models & Mechanisms · doi:10.1242/dmm.038224 · Cited by 21
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Self-citationNagano, K., Yamana, K., Saito, H., Kiviranta, R., Pedroni, A. C. F., Raval, D., Niehrs, C., Gori, F., & Baron, R. (2022) · eLife · doi:10.7554/elife.84171 · Cited by 20
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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
“The three mutations previously described in two Turkish siblings and two unrelated patients, respectively, of Japanese and Indian origin (3), were all truncating and affecting the SFRP4 netrin-like domain.”
BackgroundInfluentialKaya, 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 21
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BackgroundHigh Bone Mass Disorders: New Insights From Connecting the Clinic and the Bench
Bergen, D. J. M., Maurizi, A., Formosa, M. M., McDonald, G. L. K., El‐Gazzar, A., Hassan, N., Brandi, M. L., Riancho, J. A., Rivadeneira, F., Ntzani, E., et al. (2020) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.4715 · Cited by 17
“in Pyle’s disease (OMIM 265900), which is characterized by cortical thinning but increased trabecular bone mass.((26)) These variants in SFRP4 led to enhanced signaling in both the canonical and noncanonical arms of the pathway.”
BackgroundKındış, E., Şimşek‐Kiper, P. Ö., Koşukçu, C., Taşkıran, E. Z., Göçmen, R., Ütine, E., Haliloğlu, G., Boduroğlu, K., & Alikaşifoğlu, M. (2021) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.62179 · Cited by 14
Roles of osteoclasts in pathological conditions
Kitazawa, S., Haraguchi, R., & Kitazawa, R. (2024) · Pathology International · doi:10.1111/pin.13500 · Cited by 15
“69 In human cases of Pyle's disease, the phenotype resembles that of sFRP4 knockout mice, which exhibit thicker bones that are nonetheless fragile and susceptible to fractures.”
Marie, P. J., & Cohen-Solal, M. E. (2017) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.3356 · Cited by 15
“It was recently found that trabecular and cortical bone structures are controlled by distinct Wnt molecules,((123,124)) opening the area of novel targeted therapies for specific bone structures.”
BackgroundChoi, R. B., Bullock, W. A., Hoggatt, A. M., Horan, D. J., Pemberton, E. Z., Hong, J. M., Zhang, X., He, X., & Robling, A. G. (2020) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.4411 · Cited by 13
“This is a curious but not unexpected finding, as other genes in the Wnt pathway exhibit compartment-specific effects on the skeleton.((15-17)) The cellular/molecular mechanisms driving Notum’s compartment selectivity are not known, but conceptually they could be harnessed in a therapeutic context to selectively manipu…”
BackgroundSclerostin antibody inhibits skeletal deterioration in mice exposed to partial weight-bearing
Spatz, J., Ellman, R., Cloutier, A., Louis, L. D., van Vliet, M., Dwyer, D., Stolina, M., Ke, H. Z., & Bouxsein, M. (2017) · Life Sciences in Space Research · doi:10.1016/j.lssr.2017.01.001 · Cited by 14
Inhibition of miR-194 suppresses the Wnt/β-catenin signalling pathway in gastric cancer
Peng, Y., Zhang, X., Lin, H.-J., Deng, S., Huang, Y., Qin, Y., Feng, X.-L., Yan, R., Zhao, Y.-Q., Cheng, Y., et al. (2018) · Oncology Report · doi:10.3892/or.2018.6773 · Cited by 14
“Wnt-associated genes SFRP (29,30), nemo-like kinase (31), pygopus family PHD finger 2 (32,33), FBXW11 (34), PITX2 (35,36), FRAT genes (37) and transducer-like enhancer of split genes (38); signal transducers Dickkopf Wnt signalling pathway inhibitors (39), chibby family member 1, β -catenin antagonist (40) and kringle…”
InfluentialMoor, M. B., Ramakrishnan, S. K., Legrand, F., Dolder, S., Siegrist, M., Durussel, F., Centeno, G., Firsov, D., Hynes, N. E., Hofstetter, W., et al. (2018) · JBMR Plus · doi:10.1002/jbm4.10034 · Cited by 12
“Alternatively, disorders of the Wnt pathway have shown diverging phenotypes of cortical versus trabecular bone.((38)) In summary, a combination of both impaired growth factor signaling affecting the growth plate region and ALP dysfunction may contribute to the opposite cortical and trabecular”
BackgroundGenetics of Skeletal Disorders
Hannan, F. M., Newey, P. J., Whyte, M. P., & Thakker, R. V. (2020) · Handbook of experimental pharmacology · doi:10.1007/164_2020_350 · Cited by 12
Blouin, S., Fratzl‐Zelman, N., Roschger, A., Cabral, W. A., Klaushofer, K., Marini, J. C., Fratzl, P., & Roschger, P. (2018) · Journal of the mechanical behavior of biomedical materials/Journal of mechanical behavior of biomedical materials · doi:10.1016/j.jmbbm.2018.10.010 · Cited by 12
“[PubMed: 15388305] Simsek Kiper PO, Saito H, Gori F, Unger S, Hesse E, Yamana K, Kiviranta R, Solban N, Liu J, Brommage R, Boduroglu K, Bonafe L, Campos-Xavier B, Dikoglu E, Eastell R, Gossiel F, Harshman K, Nishimura G, Girisha KM, Stevenson BJ, Takita H, Rivolta C, Superti-Furga A, Baron R, 2016 Cortical-bone fragil…”
BackgroundThe Crucial Role of the WNT System in Bone Remodelling
Grigorie, D. (2018) · Acta Endocrinologica (Bucharest) · doi:10.4183/aeb.2018.90 · Cited by 11
“Recently it has been shown that this disease is caused by recessive mutations in the SFRP4 gene (23).”
BackgroundMashhadikhan, M., Kheiri, H., & Dehghanifard, A. (2020) · Journal of Oral Biosciences · doi:10.1016/j.job.2020.08.001 · Cited by 11
Jansen, S., Baulain, U., Habig, C., Ramzan, F., Schauer, J., Schmitt, A. O., Scholz, A. M., Sharifi, A. R., Weigend, A., & Weigend, S. (2021) · Genes · doi:10.3390/genes12050702 · Cited by 12
“The estimates ranged from −0.02 to 0.017 g/cm2 for the BMD-related SNPs and from −16.70 to 15.70 N for the markers associated with the BBS. Effects of complete dominance were observed for the SNPs AX-76044166 (MPP7), AX-75711229 (ASPN), AX-75597497 (SMAD6) and AX-76099065 (SFRP4), with one copy of the major allele mas…”
BackgroundInfluentialSun, S., Liu, Y., Sun, J., Zan, B., Cui, Y., Jin, A., Xu, H., Huang, X., Zhu, Y., Yang, Y., et al. (2024) · Bone Research · doi:10.1038/s41413-024-00353-5 · Cited by 10
“Among the screened genes, we noticed Sfrp4 , the human pathogenic gene for osteopetrosis, 31 was downregulated in Osx Cre ;R26 dn/dn osteoblasts.”
BackgroundSelf-citationThe Intricacies of Renal Phosphate Reabsorption—An Overview
Walker, V. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25094684 · Cited by 10
“Ultimately, these must be married to the renal findings to obtain a more complete picture to optimise therapy.”
BackgroundSowińska‐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
“The authors showed that sFRP-4 differentially downregulates the canonical and non-canonical Wnt signaling in both compartments of the bone, allowing for the proper bone thickness and strength (Haraguchi et al., 2016; Kiper et al., 2016; Chen et al., 2019).”
BackgroundKhouri‐Farah, N., Winchester, E. W., Schilder, B. M., Robinson, K. R., Curtis, S. W., Skene, N., Leslie, E. J., & Cotney, J. L. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.01.18.633396 · Cited by 11
Naot, D., Wilson, L. C., Allgrove, J., Adviento, E., Piec, I., Musson, D. S., Cundy, T., & Calder, A. D. (2019) · Bone · doi:10.1016/j.bone.2019.115098 · Cited by 8
Brommage, R., Liu, J., & Powell, D. R. (2023) · Bone Research · doi:10.1038/s41413-022-00242-9 · Cited by 8
“These observations are consistent with the excessively wide proximal tibiae and distal femurs previously observed in Sfrp4 KO mice.(9,20) 0 12 24 36 48”
BackgroundResultInfluentialSelf-citationMicroCT 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
Self-citationHenning, P., Movérare‐Skrtic, S., Westerlund, A., de Souza, P. P. C., Marcelino, T. F., Nilsson, K. H., Shahawy, M. E., Ohlsson, C., & Lerner, U. H. (2021) · Journal of Inflammation Research · doi:10.2147/jir.s323435 · Cited by 9
Choi, R. B., Hoggatt, A. M., Horan, D. J., Rogers, E. Z., Hong, J. M., & Robling, A. G. (2022) · Aging and Disease · doi:10.14336/ad.2022.0315 · Cited by 7
“As Wnt signaling in bone often exhibits envelope-specific effects [25, 26] which are poorly understood, other Wnt-targeted combination approaches might be available that preferentially enhance cortical effects, thus providing “designer” therapies based on the envelope to be affected [9].”
BackgroundShi, F., Yuan, G., Wu, Z., Luo, Z., Chen, Z., Liu, Q., Li, N., & Xu, R. (2025) · Journal of Orthopaedic Translation · doi:10.1016/j.jot.2025.01.010 · Cited by 8
Ohlsson, C., Farman, H. H., Gustafsson, K. L., Wu, J., Henning, P., Windahl, S. H., Sjögren, K., Gustafsson, J.-Α., Movérare‐Skrtic, S., & Lagerquist, M. K. (2020) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00018.2020 · Cited by 7
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
Xu, Y., Xie, Z., Gu, S., Zhao, X., Zhao, D., Wu, Z., Wang, J., Xu, T., Xu, R., Feng, Z., et al. (2025) · Journal of Translational Medicine · doi:10.1186/s12967-025-06798-4 · Cited by 8
Untapped opportunities for rare disease gene discovery in India
Girisha, K. M., Pande, S., Dalal, A. B., & Phadke, S. R. (2020) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.61866 · Cited by 6
“Majority publications relied on international collaborations for studies on cellular and animal models (Kiper et al., 2016; Szenker-Ravi et al., 2018) and a few of them were focussed only on strong clinical and genomic evidences (Girisha, Shukla, et al.”
BackgroundSelf-citationCraniofacial, dental, and molecular features of Pyle disease in a South African child
Chetty, M., Roomaney, I. A., Oosterwyk, C., Manyisa, N. R., Bope, C. D., Agenbag, G., & Wonkam, A. (2022) · BDJ Open · doi:10.1038/s41405-022-00120-w · Cited by 6
“Recently the secreted frizzled-related protein 4 (sFRP4), (606570) on chromosome 7p14 has been identified as a causative gene [7, 11, 12].”
BackgroundMethodInfluentialXu, 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
Signaling in Osteoblast Differentiation
Hayashi, M., Ono, T., & Nakashima, T. (2019) · Elsevier eBooks · doi:10.1016/b978-0-12-801238-3.11182-1 · Cited by 7
Wang, X., Xin, H., Ning, X., Zhang, Y., Liu, F., Zhang, Z., Jia, X., Guo, W., Hong, Y., & Sui, W. (2022) · Biomedical Materials · doi:10.1088/1748-605x/ac61fb · Cited by 5
“A recent study showed that sfrp4, an inhibitor of the Wnt pathway, can activate the noncanonical Wnt pathway when it is inhibited, thereby negatively regulating the canonical Wnt pathway [22].”
Sclerostin Inhibition in the Treatment of Osteoporosis
Baron, R., Gori, F., & Leder, B. Z. (2020) · Contemporary Endocrinology · doi:10.1007/978-3-319-69287-6_19 · Cited by 5
Self-citationGuirado, E., Villani, C., Petho, A., Chen, Y., Maienschein‐Cline, M., Lei, Z., Los, N. S., & George, A. (2023) · International Journal of Oral Science · doi:10.1038/s41368-022-00214-z · Cited by 5
“sFRP-4 has been associated with Wnt Family Member 5A (WNT5A) expression and noncanonical Wnt signaling pathway activity, as well as, activation of bone morphogenic protein (BMP) signaling and sclerostin (SOST) gene expression, contributing to decreased bone formation.(24) Indeed, patients with XLH are reported to have…”
BackgroundPyle'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
Aging Alters mRNA Processing in the Mouse Ovary
Vo, K., Pei, G. J., Thiyagarajan, R., Fields, P. E., & Rumi, M. A. K. (2025) · Cells · doi:10.3390/cells14130996 · Cited by 4
Shan, L., Liao, X., Yang, X., Zhu, E., Yuan, H., Zhou, J., Li, X., & Wang, B. (2024) · Genes & Diseases · doi:10.1016/j.gendis.2024.101209 · Cited by 4
A review of skeletal dysplasia research in India
Uttarilli, A., Shah, H. H., Shukla, A., & Girisha, K. M. (2018) · Journal of Postgraduate Medicine · doi:10.4103/jpgm.jpgm_527_17 · Cited by 4
“[62] have showed that a homozygous frameshift variation in sFRP4 gene was found to be associated with the Pyle’s disease in humans.”
Self-citation
Metadata
- Authors
- Simsek Kiper, P. O., Saito, H., Gori, F., Unger, S., Hesse, E., Yamana, K., Kiviranta, R., Solban, N., Liu, J., Brommage, R., Boduroglu, K., Bonafé, L., Campos-Xavier, B., Dikoglu, E., Eastell, R., Gossiel, F., Harshman, K., Nishimura, G., Girisha, K. M., Stevenson, B. J., Takita, H., Rivolta, C., Superti-Furga, A., & Baron, R.
- ORCID
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2016-06-30
- Volume
- 374
- Issue
- 26
- Pages
- 2553-2562
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- PMC
- PMC5070790
- OpenAlex
- W2475138245
- Cited by
- 151
- References
- 37
- Citations by year
- 2026: 12 · 2025: 9 · 2024: 10 · 2023: 11 · 2022: 13 · 2021: 18 · 2020: 18 · 2019: 22 · 2018: 21 · 2017: 16 · 2016: 1
- FWCI
- 24.37
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- edoc (University of Basel) (acceptedVersion)
- White Rose Research Online (University of Leeds, The University of Sheffield, University of York) (acceptedVersion)
- PubMed Central (acceptedVersion)
- IRIS (submittedVersion)
- Hacettepe University Institutional Repository (hacettepe.edu.tr) (submittedVersion, other-oa)
- SERVAL (Université de Lausanne) (submittedVersion)
- edoc (University of Basel)
- Funders
- Amgen
- National Institute for Health and Care Research (NF-SI-0513-10073)
- Türkiye Bilimsel ve Teknolojik Araştırma Kurumu
- Fondation Leenaards
- National Institutes of Health
- Medical Research Council (MR/K006312/1)
- Japan Society for the Promotion of Science
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR064724)
- Topics
- Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone health and osteoporosis research
- 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
- Keywords
- SFRP4, cortical bone thinning, trabecular bone, Wnt signaling, BMP signaling, sclerostin, bone homeostasis, hereditary bone disease, knockout mouse models, non-vertebral fractures
- MeSH terms
- Secreted Frizzled-Related Proteins, Adolescent, Animals, Bone and Bones, Child, Preschool, Disease Models, Animal, Female, Homeostasis, Humans, Male, Middle Aged, Osteochondrodysplasias, Proto-Oncogene Proteins, Signal Transduction, Biomarkers, Bone Density, Bone Remodeling, Gene Deletion, Sequence Analysis, DNA, Mice, Knockout, Bone Morphogenetic Proteins, Wnt Proteins, Mice
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