دورية أكاديمية
أعرض في EDS

Loss-of-function of ACVR1 in osteoblasts increases bone mass and activates canonical Wnt signaling through suppression of Wnt inhibitors SOST and DKK1.

التفاصيل البيبلوغرافية
العنوان: Loss-of-function of ACVR1 in osteoblasts increases bone mass and activates canonical Wnt signaling through suppression of Wnt inhibitors SOST and DKK1.
المؤلفون: Kamiya N; Center for Excellence in Hip Disorders, Texas Scottish Rite Hospital for Children, Dallas, TX 75219, USA. Nobby.kamiya@tsrh.org, Kaartinen VM, Mishina Y
المصدر: Biochemical and biophysical research communications [Biochem Biophys Res Commun] 2011 Oct 22; Vol. 414 (2), pp. 326-30. Date of Electronic Publication: 2011 Sep 17.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Elsevier Country of Publication: United States NLM ID: 0372516 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1090-2104 (Electronic) Linking ISSN: 0006291X NLM ISO Abbreviation: Biochem Biophys Res Commun Subsets: MEDLINE
أسماء مطبوعة: Publication: <2002- >: San Diego, CA : Elsevier
Original Publication: New York, Academic Press.
مواضيع طبية MeSH: Activin Receptors, Type I/*physiology , Bone and Bones/*anatomy & histology , Glycoproteins/*metabolism , Intercellular Signaling Peptides and Proteins/*metabolism , Osteoblasts/*enzymology , Osteogenesis/*genetics , Wnt Proteins/*metabolism, Activin Receptors, Type I/genetics ; Adaptor Proteins, Signal Transducing ; Animals ; Bone Morphogenetic Protein 7/metabolism ; Bone and Bones/enzymology ; Mice ; Mice, Transgenic ; Up-Regulation ; Wnt Proteins/antagonists & inhibitors ; Wnt Signaling Pathway
مستخلص: BMPs (Bone morphogenetic proteins) such as BMP2 and BMP7 have been used about one decade as bone anabolic agents in orthopaedics. The BMP receptor ACVR1, which is a key receptor of BMP7, is expressed in bone. The pathological role of ACVR1 in humans has been reported: a point mutation in ACVR1 can cause fibrodysplasia ossificans progressiva (FOP) in which ectopic ossification occurs in skeletal muscles and deep connective tissues. The physiological function of ACVR1 in bone, however, is totally unknown. The purpose of this study is to investigate the endogenous role of ACVR1 in osteoblasts, one of the most dominant cell-types in bone. We generated Acvr1-null mice in an osteoblast-specific manner using an inducible Cre-loxP system. Surprisingly, we found that bone mass was increased in the Acvr1-null mice. Interestingly, canonical Wnt signaling was increased and expression levels of Wnt inhibitors Sost and Dkk1 were both suppressed in the null bones during the developmental stages. In addition, we confirmed that expression levels of both Sost and Dkk1 were upregulated by BMP7 dose-dependently in vitro. These results suggest that the Acvr1-deficiency can increase bone mass by activating Wnt signaling in which both Sost and Dkk1 expression levels are diminished. This study leads to a new concept of the BMP7-ACVR1-SOST/DKK1 axis in osteoblasts, in which BMP7 signaling through ACVR1 can reduce Wnt signaling via SOST/DKK1 and then inhibits osteogenesis. Although this concept is beyond the current known function of BMP7, it can explain the varied outcomes of BMP7 treatment. We believe BMP signaling can exhibit multifaceted effects by context and cell type.
(Copyright © 2011 Elsevier Inc. All rights reserved.)
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معلومات مُعتمدة: R01DE013085 United States DE NIDCR NIH HHS; R01DE020843 United States DE NIDCR NIH HHS; R01 DE020843 United States DE NIDCR NIH HHS; R01 DE013085 United States DE NIDCR NIH HHS; R01 DE013085-12 United States DE NIDCR NIH HHS; R01 DE020843-01 United States DE NIDCR NIH HHS
المشرفين على المادة: 0 (Adaptor Proteins, Signal Transducing)
0 (Bone Morphogenetic Protein 7)
0 (Dkk1 protein, mouse)
0 (Glycoproteins)
0 (Intercellular Signaling Peptides and Proteins)
0 (Sost protein, mouse)
0 (Wnt Proteins)
0 (bmp7 protein, mouse)
EC 2.7.11.30 (Activin Receptors, Type I)
EC 2.7.11.30 (Acvr1 protein, mouse)
تواريخ الأحداث: Date Created: 20110928 Date Completed: 20111219 Latest Revision: 20211020
رمز التحديث: 20221213
مُعرف محوري في PubMed: PMC3200475
DOI: 10.1016/j.bbrc.2011.09.060
PMID: 21945937
قاعدة البيانات: MEDLINE
الوصف
تدمد:1090-2104
DOI:10.1016/j.bbrc.2011.09.060