Selective inhibition of Src family kinases by SU6656 increases bone mass by uncoupling bone formation from resorption in mice

Bone
Cyril ThouvereyJoseph Caverzasio

Abstract

Mice deficient in the non-receptor tyrosine kinase Src exhibit high bone mass due to impaired bone resorption and increased bone formation. Although several Src family kinase inhibitors inhibit bone resorption in vivo, they display variable effects on bone formation. SU6656 is a selective Src family kinase inhibitor with weaker activity towards the non-receptor tyrosine kinase Abl and receptor tyrosine kinases which are required for appropriate osteoblast proliferation, differentiation and function. Therefore, we sought to determine whether SU6656 could increase bone mass by inhibiting bone resorption and by stimulating bone formation, and to explore its mechanisms of action. Four-month-old female C57Bl/6J mice received intraperitoneal injections of either 25 mg/kg SU6656 or its vehicle every other day for 12 weeks. SU6656-treated mice exhibited increased bone mineral density, cortical thickness, cancellous bone volume and trabecular thickness. SU6656 inhibited bone resorption in mice as shown by reduced osteoclast number, and diminished expressions of Oscar, Trap5b and CtsK. SU6656 did not affect Rankl or Opg expressions. However, it blocked c-fms signaling, osteoclastogenesis and matrix resorption, and induced osteoclast apop...Continue Reading

References

Oct 1, 1992·The Journal of Clinical Investigation·B F BoyceG R Mundy
Jan 1, 1997·Annual Review of Cell and Developmental Biology·S M Thomas, J S Brugge
Dec 9, 1998·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·M JeschkeM Susa
Aug 30, 2000·Proceedings of the National Academy of Sciences of the United States of America·Y W ZhangY Ito
Oct 19, 2000·The Journal of Cell Biology·M MarziaA Teti
Nov 14, 2000·Molecular and Cellular Biology·R A BlakeS A Courtneidge
Dec 21, 2000·Trends in Pharmacological Sciences·M SusvaJ Green
Dec 19, 2003·Human Molecular Genetics·Gladys Valverde-FrancoJanet E Henderson
Oct 19, 2004·Oncogene·Sarah J Parsons, J Thomas Parsons
Oct 26, 2006·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Brendan F BoyceTomi K Sawyer
Sep 14, 2007·The Biochemical Journal·Jenny BainPhilip Cohen
Apr 9, 2008·Anti-cancer Agents in Medicinal Chemistry·Nadia RucciAnna Teti
Jan 28, 2009·Proceedings of the National Academy of Sciences of the United States of America·Hyun-Ju KimRoberta Faccio
Apr 18, 2009·Molecular Cancer Research : MCR·Teun J de VriesJenneke Klein-Nulend
Jul 15, 2009·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Shoichiro KokabuTakenobu Katagiri
Sep 25, 2009·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Rosemary A HannonRichard Eastell
Nov 19, 2009·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Evan Y YuCora N Sternberg
Mar 13, 2010·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Kate VandykeAndrew C W Zannettino
May 21, 2010·Molecular Cancer Therapeutics·Joy C YangChristopher P Evans
Dec 24, 2010·Science Signaling·Hema RangaswamiRenate B Pilz
Dec 16, 2011·The Journal of Pharmacology and Experimental Therapeutics·Richard J MurrillsPeter V N Bodine
Jan 17, 2012·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Ryuta AraiYusuke Ohba
Jan 19, 2012·Nature Communications·Barbara PeruzziAnna Teti
Mar 3, 2012·Clinical Investigation·Brendan Boyce, Lianping Xing
Aug 29, 2012·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Joseph CaverzasioCyril Thouverey
Jul 25, 2014·Journal of Cellular Physiology·Jiro TakitoMasanori Nakamura
Mar 25, 2015·Molecular and Cellular Endocrinology·You Hee ChoiKwang Youl Lee
Dec 9, 2015·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Cyril Thouverey, Joseph Caverzasio

❮ Previous
Next ❯

Citations


❮ Previous
Next ❯

Related Concepts

Related Feeds

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis

Cell Signaling by Tyrosine Kinases

Receptor tyrosine kinases (RTKs) are the high-affinity cell surface receptors for many polypeptide growth factors, cytokines, and hormones. RTKs have been shown not only to be key regulators of normal cellular processes but also to have a critical role in the development and progression of many types of cancer. Discover the latest research on cell signaling and RTK here.

Related Papers

Osteoporosis International : a Journal Established As Result of Cooperation Between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA
H XieE-Y Liao
Proceedings of the National Academy of Sciences of the United States of America
Marc Baud'huinPeter I Croucher
© 2022 Meta ULC. All rights reserved