Osteoclast-secreted SLIT3 coordinates bone resorption and formation

The Journal of Clinical Investigation
Beom-Jun KimJung-Min Koh

Abstract

Coupling is the process that links bone resorption to bone formation in a temporally and spatially coordinated manner within the remodeling cycle. Several lines of evidence point to the critical roles of osteoclast-derived coupling factors in the regulation of osteoblast performance. Here, we used a fractionated secretomic approach and identified the axon-guidance molecule SLIT3 as a clastokine that stimulated osteoblast migration and proliferation by activating β-catenin. SLIT3 also inhibited bone resorption by suppressing osteoclast differentiation in an autocrine manner. Mice deficient in Slit3 or its receptor, Robo1, exhibited osteopenic phenotypes due to a decrease in bone formation and increase in bone resorption. Mice lacking Slit3 specifically in osteoclasts had low bone mass, whereas mice with either neuron-specific Slit3 deletion or osteoblast-specific Slit3 deletion had normal bone mass, thereby indicating the importance of SLIT3 as a local determinant of bone metabolism. In postmenopausal women, higher circulating SLIT3 levels were associated with increased bone mass. Notably, injection of a truncated recombinant SLIT3 markedly rescued bone loss after an ovariectomy. Thus, these results indicate that SLIT3 plays an ...Continue Reading

References

Jul 12, 2002·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Romain DacquinGérard Karsenty
Feb 6, 2003·International Journal of Cancer. Journal International Du Cancer·Takeshi KashimaAgamemnon E Grigoriadis
Apr 19, 2003·Proceedings of the National Academy of Sciences of the United States of America·Wenlin YuanDavid M Ornitz
May 8, 2004·Developmental Cell·Uta GrieshammerGail R Martin
Mar 10, 2005·Proceedings of the National Academy of Sciences of the United States of America·Hailan HuGreg J Bashaw
Aug 3, 2005·The Journal of Experimental Medicine·Mitsuru YagiToshio Suda
May 4, 2006·The Journal of Clinical Investigation·Venkatesh KrishnanOrmond A Macdougald
Aug 8, 2006·Cell Metabolism·Chen ZhaoKoichi Matsuo
Aug 21, 2007·Acta Crystallographica. Section D, Biological Crystallography·Cecile MorlotAndrew A McCarthy
Oct 10, 2007·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Yongqiang WangMichael Glogauer
Apr 15, 2008·Archives of Biochemistry and Biophysics·Koichi Matsuo, Naoko Irie
Jul 8, 2008·Journal of Neuroendocrinology·S Takeda
Jul 31, 2008·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Emma C WalkerNatalie A Sims
Nov 7, 2008·Human Genetics·T Segovia-SilvestreK Henriksen
Dec 17, 2008·Proceedings of the National Academy of Sciences of the United States of America·Larry PedersonMerry Jo Oursler
Aug 13, 2010·Nature·Simón Méndez-FerrerPaul S Frenette
Oct 13, 2010·Annual Review of Pathology·Xu Feng, Jay M McDonald
Nov 17, 2010·The Journal of Immunology : Official Journal of the American Association of Immunologists·Sacha B GeutskensPaula B van Hennik
Apr 24, 2012·Nature·Mikihito HayashiHiroshi Takayanagi
May 12, 2012·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Eric HaÿPierre J Marie
Aug 29, 2012·Proceedings of the National Academy of Sciences of the United States of America·Nicolas BonnetSerge L Ferrari
Dec 1, 2012·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·David W DempsterA Michael Parfitt
Jan 17, 2013·The Journal of Clinical Investigation·Sutada LotinunRoland Baron
May 7, 2013·Nature·Toru FukudaHiroshi Itoh
May 24, 2013·Calcified Tissue International·Kim HenriksenT John Martin
Aug 3, 2013·The Journal of Clinical Investigation·Sunao TakeshitaKyoji Ikeda
Jan 1, 2012·BoneKEy Reports·Takako Negishi-Koga, Hiroshi Takayanagi
Jan 29, 2014·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Kazuhiko MatsuokaSunao Takeshita

❮ Previous
Next ❯

Citations

Mar 6, 2018·The Journal of Clinical Investigation·Jameel IqbalMone Zaidi
Oct 30, 2018·Journal of Orthopaedic Research : Official Publication of the Orthopaedic Research Society·Chelsea S BahneyKurt D Hankenson
Feb 1, 2019·The Journal of Biological Chemistry·Naoka YamamotoTomoaki Niimi
Oct 8, 2019·Tissue Engineering. Part B, Reviews·Dan WangGregory M Cooper
Dec 28, 2019·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Bongjin ShinSun-Kyeong Lee
Sep 26, 2019·Annual Review of Physiology·Natalie A Sims, T John Martin
Feb 12, 2020·Scientific Reports·Young-Sun LeeJung-Min Koh
Aug 9, 2020·Gynecological Endocrinology : the Official Journal of the International Society of Gynecological Endocrinology·Alberto Hidalgo-BravoRafael Velázquez-Cruz
Jun 9, 2020·Chonnam Medical Journal·Jung Ha Kim, Nacksung Kim
Mar 25, 2020·Endocrinology and Metabolism·Beom Jun KimJung Min Koh
Mar 20, 2020·BioMed Research International·Haixing WangZiqing Li
Mar 7, 2020·Bone Research·Na LiMatthew B Greenblatt
Aug 19, 2020·Nature Communications·Vikrant K BhosleLisa A Robinson
Dec 6, 2018·Cellular and Molecular Life Sciences : CMLS·Beom-Jun Kim, Jung-Min Koh
Dec 22, 2020·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Alexandra RafipayNeil Vargesson
Nov 20, 2020·Bone·Megan M WeivodaDavid G Monroe
Jan 16, 2021·Cell Proliferation·Jiankang ZhangWei Jing
Dec 12, 2020·Frontiers in Cell and Developmental Biology·Hui PengTing Wen
Nov 27, 2020·Frontiers in Cell and Developmental Biology·Jin Young LeeBeom-Jun Kim
Feb 19, 2021·Bone Research·Na LiMatthew B Greenblatt
Sep 6, 2020·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Danqi YaoXiao Zhu
Apr 16, 2021·Advanced Science·Qian-Qian WanKai Jiao
Apr 15, 2021·Endocrinology and Metabolism·Da Ae KimBeom-Jun Kim
May 6, 2021·International Journal of Molecular Sciences·Jin-Young LeeBeom-Jun Kim
May 20, 2021·Journal of Orthopaedic Surgery and Research·Guo LiJiQiang Duan
Aug 24, 2021·Journal of Cachexia, Sarcopenia and Muscle·Han Jin ChoJung-Min Koh

❮ Previous
Next ❯

Methods Mentioned

BETA
ELISA
PCR
transfection
GTPases
GTPase
transcription profiling

Software Mentioned

Histometry
BIOQUANT
GraphPad PRISM
Skyscan
Mascot
SPSS
SLIT3

Related Concepts

Related Feeds

Adherens Junctions

An adherens junction is defined as a cell junction whose cytoplasmic face is linked to the actin cytoskeleton. They can appear as bands encircling the cell (zonula adherens) or as spots of attachment to the extracellular matrix (adhesion plaques). Adherens junctions uniquely disassemble in uterine epithelial cells to allow the blastocyst to penetrate between epithelial cells. Discover the latest research on adherens junctions here.

Cadherins and Catenins

Cadherins (named for "calcium-dependent adhesion") are a type of cell adhesion molecule (CAM) that is important in the formation of adherens junctions to bind cells with each other. Catenins are a family of proteins found in complexes with cadherin cell adhesion molecules of animal cells: alpha-catenin can bind to β-catenin and can also bind actin. β-catenin binds the cytoplasmic domain of some cadherins. Discover the latest research on cadherins and catenins here.

Related Papers

Nature
Mikihito HayashiHiroshi Takayanagi
Biochemical and Biophysical Research Communications
Ryotaro IwasakiTakeshi Miyamoto
Endocrine Research
Sakarat N PramojaneeSiriporn C Chattipakorn
© 2021 Meta ULC. All rights reserved