The DOI matches its Crossref record; 8 of the 8 references it cites were found in a registry or an index.
Lrp5 Controls Bone Formation by Inhibiting Serotonin Synthesis in the Duodenum
Open accessAbstract
Loss- and gain-of-function mutations in the broadly expressed gene Lrp5 affect bone formation causing osteoporosis and high bone mass, respectively. Although Lrp5 is viewed as a Wnt coreceptor osteoblast-specific disruption of β-Catenin does not affect bone formation. Instead, we show here that Lrp5 inhibits expression of Tph1, the rate-limiting biosynthetic enzyme for serotonin in enterochromaffin cells of the duodenum. Accordingly, decreasing serotonin blood levels normalizes bone formation and bone mass in Lrp5-deficient mice and gut- but not osteoblast-specific Lrp5 inactivation decreases bone formation in a β-Catenin–independent manner. Moreover, gut-specific activation of Lrp5, or inactivation of Tph1, increases bone mass and prevents ovariectomy-induced bone loss. Serotonin acts on osteoblasts through the Htr1b receptor and CREB to inhibit their proliferation. By identifying duodenum-derived serotonin as a hormone inhibiting bone formation in an Lrp5-dependent manner this study broadens our understanding of bone remodeling and suggests novel therapies to increase bone mass.
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Cites
Leptin Inhibits Bone Formation through a Hypothalamic Relay
Ducy, P., Amling, M., Takeda, S., Priemel, M., Schilling, A. F., Beil, F. T., Shen, J., Vinson, C., Rueger, J. M., & Karsenty, G. (2000) · Cell · doi:10.1016/s0092-8674(00)81558-5 · Cited by 2,077
Self-citationWNT and β-catenin signalling: diseases and therapies
Moon, R. T., Kohn, A. D., Ferrari, G. V. D., & Kaykas, A. (2004) · Nature Reviews Genetics · doi:10.1038/nrg1427 · Cited by 1,763
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
Self-citationRegulation of bone mass by Wnt signaling
Krishnan, V. (2006) · Journal of Clinical Investigation · doi:10.1172/jci28551 · Cited by 1,407
Kato, M., Patel, M. S., Levasseur, R., Lobov, I., Chang, B. H.-J., Glass, D. A., Hartmann, C., Li, L., Hwang, T.-H., Brayton, C. F., et al. (2002) · The Journal of Cell Biology · doi:10.1083/jcb.200201089 · Cited by 1,086
Self-citationSkeletal remodeling in health and disease
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Disruption of CREB function in brain leads to neurodegeneration
Mantamadiotis, T., Lemberger, T., Bleckmann, S. C., Kern, H., Kretz, O., Villalba, A. M., Tronche, F., Kellendonk, C., Gau, D., Kapfhammer, J., et al. (2002) · Nature Genetics · doi:10.1038/ng882 · Cited by 684
Self-citationReduced bone cortical thickness in boys with autism or autism spectrum disorder
Hediger, M. L., England, L. J., Molloy, C. A., Yu, K. F., Manning-Courtney, P., & Mills, J. L. (2008) · Journal of Autism and Developmental Disorders · doi:10.1007/s10803-007-0453-6 · Cited by 193
Cited by
Wnt/β-Catenin Signaling: Components, Mechanisms, and Diseases
MacDonald, B. T., Tamai, K., & He, X. (2009) · Developmental Cell · doi:10.1016/j.devcel.2009.06.016 · Cited by 5,583
The gut microbiota--masters of host development and physiology
Sommer, F., & Bäckhed, F. (2013) · Nature Reviews Microbiology · doi:10.1038/nrmicro2974 · Cited by 3,681
Indigenous bacteria from the gut microbiota regulate host serotonin biosynthesis
Yano, J. M., Yu, K., Donaldson, G. P., Shastri, G. G., Ann, P., Ma, L., Nagler, C. R., Ismagilov, R. F., Mazmanian, S. K., & Hsiao, E. Y. (2015) · Cell · doi:10.1016/j.cell.2015.02.047 · Cited by 3,614
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
Serotonin signalling in the gut: functions, dysfunctions and therapeutic targets
Mawe, G. M., & Hoffman, J. M. (2013) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/nrgastro.2013.105 · Cited by 1,165
Metadata
- Authors
- Yadav, V. K., Ryu, J.-H., Suda, N., Tanaka, K. F., Gingrich, J. A., Schütz, G., Glorieux, F. H., Chiang, C. Y., Zajac, J. D., Insogna, K. L., Mann, J. J., Hen, R., Ducy, P., & Karsenty, G.
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2008-11
- Volume
- 135
- Issue
- 5
- Pages
- 825-837
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2073052871
- Cited by
- 834
- References
- 8
- FWCI
- 31.64
- Type
- journal article
- Language
- en
- Open access
- bronze
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