Lrp4 in osteoblasts suppresses bone formation and promotes osteoclastogenesis and bone resorption

Proceedings of the National Academy of Sciences of the United States of America
Lei XiongWen-Cheng Xiong

Abstract

Bone mass is maintained by balanced activity of osteoblasts and osteoclasts. Lrp4 (low-density lipoprotein receptor related protein 4) is a member of the LDL receptor family, whose mutations have been identified in patients with high-bone-mass disorders, such as sclerosteosis and van Buchem diseases. However, it remains unknown whether and how Lrp4 regulates bone-mass homeostasis in vivo. Here we provide evidence that Lrp4-null mutation or specific mutation in osteoblast-lineage cells increased cortical and trabecular bone mass, which was associated with elevated bone formation and impaired bone resorption. This phenotype was not observed in osteoclast-selective Lrp4 knockout mice. Mechanistic studies indicate that loss of Lrp4 function in osteoblast-lineage cells increased serum levels of sclerostin, a key factor for bone-mass homeostasis that interacts with Lrp4, but abolished the inhibition of Wnt/β-catenin signaling and osteoblastic differentiation by sclerostin. Concomitantly, sclerostin induction of RANKL (receptor activator of nuclear kappa B ligand) was impaired, leading to a lower ratio of RANKL over OPG (osteoprotegerin) (a key factor for osteoclastogenesis). Taken together, these results support the view for Lrp4 as ...Continue Reading

References

Sep 1, 1988·Proceedings of the National Academy of Sciences of the United States of America·M CrossR Renkawitz
May 9, 1998·Proceedings of the National Academy of Sciences of the United States of America·H YasudaT Suda
Sep 1, 2000·Science·S L Teitelbaum
Nov 24, 2001·Cell·Y GongUNKNOWN Osteoporosis-Pseudoglioma Syndrome Collaborative Group
May 17, 2002·The New England Journal of Medicine·Lynn M BoydenRichard P Lifton
Mar 17, 2004·The Journal of Experimental Medicine·Rutger L van BezooijenClemens W G M Löwik
Mar 22, 2005·The Journal of Biological Chemistry·Xiaofeng LiDianqing Wu
May 4, 2005·Developmental Cell·Donald A GlassGerard Karsenty
May 24, 2005·The Journal of Biological Chemistry·Mikhail SemënovXi He
Dec 7, 2005·The Journal of Clinical Endocrinology and Metabolism·Susan M Ott
Nov 23, 2006·Development·Scott D WeatherbeeLee A Niswander
Feb 14, 2007·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Wendy BalemansWim Van Hul
Oct 14, 2008·Cell·Natalie KimSteven J Burden
Oct 30, 2008·Neuron·Bin ZhangLin Mei
Apr 8, 2011·The Journal of Biological Chemistry·Olivier LeupinMichaela Kneissel
Feb 8, 2013·Nature Medicine·Roland Baron, Michaela Kneissel
May 3, 2013·American Journal of Medical Genetics. Part a·Ariana KariminejadBernd Wollnik
May 15, 2013·European Journal of Medical Genetics·Tahir Naeem KhanN Dahl
Sep 3, 2013·Developmental Biology·Nicole M ColletteGabriela G Loots
Jun 14, 2014·American Journal of Medical Genetics. Part a·Amanda S LindyMichael J Friez
Nov 19, 2014·Proceedings of the National Academy of Sciences of the United States of America·Ming-Kang ChangMichaela Kneissel

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Citations

Feb 5, 2016·Biochemical and Biophysical Research Communications·Dongdong ZhangSung Kil Lim
Dec 30, 2015·Journal of Biochemistry·Yasuhiro KobayashiNaoyuki Takahashi
Oct 18, 2015·Rheumatic Diseases Clinics of North America·Jennifer L Barnas, Christopher T Ritchlin
Jan 12, 2016·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Igor FijalkowskiEveline Boudin
Apr 8, 2016·Nature Reviews. Rheumatology·David KarasikMark L Johnson
Jul 15, 2015·BoneKEy Reports·Yasuhiro KobayashiNaoyuki Takahashi
May 21, 2016·Mediators of Inflammation·Chen Chao WeiChe Tao
Jun 1, 2017·European Journal of Medical Genetics·Muhammad AfzalRicarda Flöttmann
Jan 16, 2019·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Bo WangWen-Cheng Xiong
Oct 26, 2018·Journal of Bone and Mineral Metabolism·Masanori Koide, Yasuhiro Kobayashi
Jan 30, 2018·Annals of the New York Academy of Sciences·Min YanLin Mei
Sep 6, 2018·Nature Reviews. Endocrinology·Natasha M Appelman-Dijkstra, Socrates E Papapoulos
Dec 4, 2019·Nature Reviews. Endocrinology·Tie-Lin YangHong-Wen Deng
May 10, 2017·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Eveline BoudinWim Van Hul
Nov 9, 2019·International Journal of Molecular Sciences·Kazuhiro MaedaKeishi Marumo
Jun 2, 2020·PLoS Biology·Lei XiongWen-Cheng Xiong
May 29, 2018·International Journal of Endocrinology·Sarah-Kim BissonFabrice Mac-Way
Sep 29, 2020·Risk Management and Healthcare Policy·Agnieszka Turoń-SkrzypińskaIwona Rotter
Jul 18, 2020·Cancer Biomarkers : Section a of Disease Markers·Zhijun MaoJing Zhu
Oct 5, 2021·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Soohyun P KimRyan C Riddle
Dec 4, 2021·Journal of Human Genetics·Hammal KhanWasim Ahmad

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