Control of bone formation by the serpentine receptor Frizzled-9

Author:

Albers Joachim1,Schulze Jochen1,Beil F. Timo1,Gebauer Matthias1,Baranowsky Anke1,Keller Johannes1,Marshall Robert P.1,Wintges Kristofer1,Friedrich Felix W.1,Priemel Matthias1,Schilling Arndt F.1,Rueger Johannes M.1,Cornils Kerstin1,Fehse Boris1,Streichert Thomas1,Sauter Guido1,Jakob Franz2,Insogna Karl L.3,Pober Barbara4,Knobeloch Klaus-Peter5,Francke Uta6,Amling Michael1,Schinke Thorsten1

Affiliation:

1. Department of Osteology and Biomechanics, Department of Trauma, Hand, and Reconstructive Surgery, Department for Stem Cell Transplantation, Institute of Clinical Chemistry, and Department of Pathology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany

2. Orthopedic Department, University of Würzburg, 97074 Würzburg, Germany

3. Department of Internal Medicine, Yale School of Medicine, New Haven, CT 06519

4. Department of Pediatrics, Massachusetts General Hospital, Boston, MA 02114

5. Department of Neuropathology, University Clinic Freiburg, Freiburg 79106, Germany

6. Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305

Abstract

Although Wnt signaling in osteoblasts is of critical importance for the regulation of bone remodeling, it is not yet known which specific Wnt receptors of the Frizzled family are functionally relevant in this process. In this paper, we show that Fzd9 is induced upon osteoblast differentiation and that Fzd9−/− mice display low bone mass caused by impaired bone formation. Our analysis of Fzd9−/− primary osteoblasts demonstrated defects in matrix mineralization in spite of normal expression of established differentiation markers. In contrast, we observed a reduced expression of chemokines and interferon-regulated genes in Fzd9−/− osteoblasts. We also identified the ubiquitin-like modifier Isg15 as one potential downstream mediator of Fzd9 in these cells. Importantly, our molecular analysis further revealed that canonical Wnt signaling is not impaired in the absence of Fzd9, thus explaining the absence of a bone resorption phenotype. Collectively, our results reveal a previously unknown function of Fzd9 in osteoblasts, a finding that may have therapeutic implications for bone loss disorders.

Publisher

Rockefeller University Press

Subject

Cell Biology

Cited by 98 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3