The DOI matches its Crossref record; 43 of the 43 references it cites were found in a registry or an index.
A bispecific antibody targeting sclerostin and DKK-1 promotes bone mass accrual and fracture repair
Open accessAbstract
Inhibition of the Wnt antagonist sclerostin increases bone mass in patients with osteoporosis and in preclinical animal models. Here we show increased levels of the Wnt antagonist Dickkopf-1 (DKK-1) in animals treated with sclerostin antibody, suggesting a negative feedback mechanism that limits Wnt-driven bone formation. To test our hypothesis that co-inhibition of both factors further increases bone mass, we engineer a first-in-class bispecific antibody with single residue pair mutations in the Fab region to promote efficient and stable cognate light–heavy chain pairing. We demonstrate that dual inhibition of sclerostin and DKK-1 leads to synergistic bone formation in rodents and non-human primates. Furthermore, by targeting distinct facets of fracture healing, the bispecific antibody shows superior bone repair activity compared with monotherapies. This work supports the potential of this agent both for treatment and prevention of fractures and offers a promising therapeutic approach to reduce the burden of low bone mass disorders.
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Cites
The interpretation of protein structures: Estimation of static accessibility
Lee, B., & Richards, F. M. (1971) · Journal of Molecular Biology · doi:10.1016/0022-2836(71)90324-x · Cited by 5,850
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
Sclerostin Binds to LRP5/6 and Antagonizes Canonical Wnt Signaling
Li, X., Zhang, Y., Kang, H., Liu, W., Liu, P., Zhang, J., Harris, S. E., & Wu, D. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m413274200 · Cited by 1,366 · cited 3×
“The qRT-PCR amplification program was: (1) activation at 50 C for 2min; (2) denaturation at 95 C for 10min; (3) amplification 40 cycles at 95 C for 15 s and at 60 C for 1min with fluorescence capture at each step (ABI PRISM 7900HT Sequence Detection Systems, Applied Biosystems, Foster City, CA).”
BackgroundMethodSelf-citationMechanical Stimulation of Bone in Vivo Reduces Osteocyte Expression of Sost/Sclerostin
Robling, A. G., Niziolek, P. J., Baldridge, L. A., Condon, K. W., Allen, M. R., Alam, I., Mantila, S. M., Gluhak-Heinrich, J., Bellido, T. M., Harris, S. E., et al. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m705092200 · Cited by 1,350
Romosozumab in Postmenopausal Women with Low Bone Mineral Density
McClung, M. R., Grauer, A., Boonen, S., Bolognese, M. A., Brown, J. P., Diez-Perez, A., Langdahl, B. L., Reginster, J.-Y., Zanchetta, J. R., Wasserman, S. M., et al. (2014) · New England Journal of Medicine · doi:10.1056/nejmoa1305224 · Cited by 1,258
Estrada, K., Styrkarsdottir, U., Evangelou, E., Hsu, Y.-H., Duncan, E. L., Ntzani, E. E., Oei, L., Albagha, O. M. E., Amin, N., Kemp, J. P., et al. (2012) · Nature Genetics · doi:10.1038/ng.2249 · Cited by 1,174
Brunkow, M. E., Gardner, J. C., Van Ness, J., Paeper, B. W., Kovacevich, B. R., Proll, S., Skonier, J. E., Zhao, L., Sabo, P. J., Fu, Y.-H., et al. (2001) · The American Journal of Human Genetics · doi:10.1086/318811 · Cited by 1,011
Li, X., Ominsky, M. S., Niu, Q.-T., Sun, N., Daugherty, B., D'Agostin, D., Kurahara, C., Gao, Y., Cao, J., Gong, J., et al. (2008) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.080216 · Cited by 936
Self-citationvan Bezooijen, R. L., Roelen, B. A. J., Visser, A., van der Wee-Pals, L., de Wilt, E., Karperien, M., Hamersma, H., Papapoulos, S. E., ten Dijke, P., & Löwik, C. W. G. M. (2004) · The Journal of Experimental Medicine · doi:10.1084/jem.20031454 · Cited by 892
Single-dose, placebo-controlled, randomized study of AMG 785, a sclerostin monoclonal antibody
Padhi, D., Jang, G., Stouch, B., Fang, L., & Posvar, E. (2011) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.173 · Cited by 786
Cited by
Osteoporosis treatment: recent developments and ongoing challenges
Khosla, S., & Hofbauer, L. C. (2017) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(17)30188-2 · Cited by 1,019
Ho-Shui-Ling, A., Bolander, J., Rustom, L. E., Johnson, A. W., Luyten, F. P., & Picart, C. (2018) · Biomaterials · doi:10.1016/j.biomaterials.2018.07.017 · Cited by 961
Wnt/β-catenin signaling components and mechanisms in bone formation, homeostasis, and disease
Hu, L., Chen, W., Qian, A., & Li, Y.-P. (2024) · Bone Research · doi:10.1038/s41413-024-00342-8 · Cited by 359
Interleukin-6 Interweaves the Bone Marrow Microenvironment, Bone Loss, and Multiple Myeloma
Harmer, D., Falank, C., & Reagan, M. R. (2019) · Frontiers in Endocrinology · doi:10.3389/fendo.2018.00788 · Cited by 307
Bispecific antibodies: design, therapy, perspectives
Sedykh, S., Prinz, V., Buneva, V., & Nevinsky, G. (2018) · Drug Design, Development and Therapy · doi:10.2147/dddt.s151282 · Cited by 292
Metadata
- Authors
- Florio, M., Gunasekaran, K., Stolina, M., Li, X., Liu, L., Tipton, B., Salimi-Moosavi, H., Asuncion, F. J., Li, C., Sun, B., Tan, H. L., Zhang, L., Han, C.-Y., Case, R., Duguay, A. N., Grisanti, M., Stevens, J., Pretorius, J. K., Pacheco, E., Jones, H., Chen, Q., Soriano, B. D., Wen, J., Heron, B., Jacobsen, F. W., Brisan, E., Richards, W. G., Ke, H. Z., & Ominsky, M. S.
- Venue
- Nature Communications
- Published
- 2016-05-27
- Volume
- 7
- Issue
- 1
- Pages
- 11505-11505
- ISSN
- 2041-1723 (ISSN-L)
- OpenAlex
- W2398309765
- Cited by
- 257
- References
- 43
- FWCI
- 34.20
- Type
- journal article
- Language
- en
- Open access
- gold
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- Florio, M., Gunasekaran, K., Stolina, M., Li, X., Liu, L., Tipton, B., Salimi-Moosavi, H., Asuncion, F. J., Li, C., Sun, B., Tan, H. L., Zhang, L., Han, C.-Y., Case, R., Duguay, A. N., Grisanti, M., Stevens, J., Pretorius, J. K., Pacheco, E., . . . Ominsky, M. S. (2016). A bispecific antibody targeting sclerostin and DKK-1 promotes bone mass accrual and fracture repair. Nature Communications. https://doi.org/10.1038/ncomms11505
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
