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Canonical Wnt signaling in differentiated osteoblasts controls osteoclast differentiation.
Dev Cell. 2005 May; 8(5):751-64.DC

Abstract

Inactivation of beta-catenin in mesenchymal progenitors prevents osteoblast differentiation; inactivation of Lrp5, a gene encoding a likely Wnt coreceptor, results in low bone mass (osteopenia) by decreasing bone formation. These observations indicate that Wnt signaling controls osteoblast differentiation and suggest that it may regulate bone formation in differentiated osteoblasts. Here, we study later events and find that stabilization of beta-catenin in differentiated osteoblasts results in high bone mass, while its deletion from differentiated osteoblasts leads to osteopenia. Surprisingly, histological analysis showed that these mutations primarily affect bone resorption rather than bone formation. Cellular and molecular studies showed that beta-catenin together with TCF proteins regulates osteoblast expression of Osteoprotegerin, a major inhibitor of osteoclast differentiation. These findings demonstrate that beta-catenin, and presumably Wnt signaling, promote the ability of differentiated osteoblasts to inhibit osteoclast differentiation; thus, they broaden our knowledge of the functions Wnt proteins have at various stages of skeletogenesis.

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Authors+Show Affiliations

Glass DA
Department of Molecular and Human Genetics, Bone Disease Program of Texas, Houston, 77030, USA.
Bialek P
No affiliation info available
Ahn JD
No affiliation info available
Starbuck M
No affiliation info available
Patel MS
No affiliation info available
Clevers H
No affiliation info available
Taketo MM
No affiliation info available
Long F
No affiliation info available
McMahon AP
No affiliation info available
Lang RA
No affiliation info available
Karsenty G
No affiliation info available

MeSH

AnimalsBone DevelopmentCell DifferentiationCytoskeletal ProteinsGene Expression Regulation, DevelopmentalGlycoproteinsIn Situ HybridizationIntercellular Signaling Peptides and ProteinsLDL-Receptor Related ProteinsLac OperonLow Density Lipoprotein Receptor-Related Protein-5MiceMice, KnockoutMice, Mutant StrainsMice, TransgenicOsteoblastsOsteoclastsOsteogenesisOsteopetrosisOsteoprotegerinReceptors, Cytoplasmic and NuclearReceptors, LDLReceptors, Tumor Necrosis FactorSignal TransductionTrans-ActivatorsWnt Proteinsbeta Catenin

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

15866165

Citation

Glass, Donald A., et al. "Canonical Wnt Signaling in Differentiated Osteoblasts Controls Osteoclast Differentiation." Developmental Cell, vol. 8, no. 5, 2005, pp. 751-64.
Glass DA, Bialek P, Ahn JD, et al. Canonical Wnt signaling in differentiated osteoblasts controls osteoclast differentiation. Dev Cell. 2005;8(5):751-64.
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., & Karsenty, G. (2005). Canonical Wnt signaling in differentiated osteoblasts controls osteoclast differentiation. Developmental Cell, 8(5), 751-64.
Glass DA, et al. Canonical Wnt Signaling in Differentiated Osteoblasts Controls Osteoclast Differentiation. Dev Cell. 2005;8(5):751-64. PubMed PMID: 15866165.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Canonical Wnt signaling in differentiated osteoblasts controls osteoclast differentiation. AU - Glass,Donald A,2nd AU - Bialek,Peter, AU - Ahn,Jong Deok, AU - Starbuck,Michael, AU - Patel,Millan S, AU - Clevers,Hans, AU - Taketo,Mark M, AU - Long,Fanxin, AU - McMahon,Andrew P, AU - Lang,Richard A, AU - Karsenty,Gerard, PY - 2004/12/04/received PY - 2005/01/31/revised PY - 2005/02/16/accepted PY - 2005/5/4/pubmed PY - 2005/6/24/medline PY - 2005/5/4/entrez SP - 751 EP - 64 JF - Developmental cell JO - Dev Cell VL - 8 IS - 5 N2 - Inactivation of beta-catenin in mesenchymal progenitors prevents osteoblast differentiation; inactivation of Lrp5, a gene encoding a likely Wnt coreceptor, results in low bone mass (osteopenia) by decreasing bone formation. These observations indicate that Wnt signaling controls osteoblast differentiation and suggest that it may regulate bone formation in differentiated osteoblasts. Here, we study later events and find that stabilization of beta-catenin in differentiated osteoblasts results in high bone mass, while its deletion from differentiated osteoblasts leads to osteopenia. Surprisingly, histological analysis showed that these mutations primarily affect bone resorption rather than bone formation. Cellular and molecular studies showed that beta-catenin together with TCF proteins regulates osteoblast expression of Osteoprotegerin, a major inhibitor of osteoclast differentiation. These findings demonstrate that beta-catenin, and presumably Wnt signaling, promote the ability of differentiated osteoblasts to inhibit osteoclast differentiation; thus, they broaden our knowledge of the functions Wnt proteins have at various stages of skeletogenesis. SN - 1534-5807 UR - https://www.unboundmedicine.com/medline/citation/15866165/Canonical_Wnt_signaling_in_differentiated_osteoblasts_controls_osteoclast_differentiation_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1534-5807(05)00097-3 DB - PRIME DP - Unbound Medicine ER -