The PI3K pathway regulates endochondral bone growth through control of hypertrophic chondrocyte differentiation.

BMC Developmental Biology
Veronica UliciF Beier

Abstract

The majority of our bones develop through the process of endochondral ossification that involves chondrocyte proliferation and hypertrophic differentiation in the cartilage growth plate. A large number of growth factors and hormones have been implicated in the regulation of growth plate biology, however, less is known about the intracellular signaling pathways involved. PI3K/Akt has been identified as a major regulator of cellular proliferation, differentiation and death in multiple cell types. Employing an organ culture system of embryonic mouse tibiae and LY294002, a pharmacological inhibitor of PI3K, we show that inhibition of the pathway results in significant growth reduction, demonstrating that PI3K is required for normal endochondral bone growth in vitro. PI3K inhibition reduces the length of the proliferating and particularly of the hypertrophic zone. Studies with organ cultures and primary chondrocytes in micromass culture show delayed hypertrophic differentiation of chondrocytes and increased apoptosis in the presence of LY294002. Surprisingly, PI3K inhibition had no strong effect on IGF1-induced bone growth, but partially blocked the anabolic effects of C-type natriuretic peptide. Our data demonstrate an essential ro...Continue Reading

References

Apr 8, 1998·Current Opinion in Genetics & Development·D R Alessi, P Cohen
Aug 17, 1999·The Journal of Clinical Investigation·B LanskeH M Kronenberg
Nov 2, 1999·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·J WangC A Bondy
Dec 2, 1999·Experimental Cell Research·B Vanhaesebroeck, M D Waterfield
Dec 2, 1999·Genes & Development·S R DattaM E Greenberg
May 9, 2000·Frontiers in Bioscience : a Journal and Virtual Library·P LuValle, F Beier
Mar 22, 2001·Proceedings of the National Academy of Sciences of the United States of America·H ChushoK Nakao
Mar 30, 2001·Novartis Foundation Symposium·G Karsenty
Sep 5, 2001·Current Opinion in Genetics & Development·E F Wagner, G Karsenty
Nov 1, 2001·Annual Review of Cell and Developmental Biology·R KatsoM D Waterfield
Nov 16, 2002·Journal of Bone and Mineral Metabolism·Yasato KomatsuKazuwa Nakao
Jan 31, 2003·The Journal of Biological Chemistry·Veronica GalvanDale E Bredesen
Apr 2, 2003·Nature Reviews. Immunology·Klaus Okkenhaug, Bart Vanhaesebroeck
May 15, 2003·Archives of Biochemistry and Biophysics·Lazaros C Foukas, Klaus Okkenhaug
May 16, 2003·Nature·Henry M Kronenberg
Sep 6, 2003·Birth Defects Research. Part C, Embryo Today : Reviews·Lillian ShumRocky S Tuan
Nov 5, 2003·The Biochemical Journal·Lee-Anne StantonFrank Beier
Jan 17, 2004·The Journal of Biological Chemistry·Guoyan WangFrank Beier
Jan 31, 2004·Bone·Lauren H Golden, Karl L Insogna
Feb 3, 2004·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Matthew C StewartR Tracy Ballock
Dec 14, 2004·Immunologic Research·Rahul K Patel, Chandra Mohan
Dec 30, 2004·Journal of Molecular and Cellular Cardiology·Takashi Matsui, Anthony Rosenzweig
Jan 25, 2005·The Journal of Biological Chemistry·Anita WoodsFrank Beier
Feb 5, 2005·Cell Communication and Signaling : CCS·Gwendolen C ReillyPhoebe S Leboy
Feb 8, 2005·Biochemical and Biophysical Research Communications·Sylvain Provot, Ernestina Schipani
Jul 23, 2005·The Journal of Biological Chemistry·Enzo CalauttiPaul F Goetinck
Dec 13, 2005·Nature Reviews. Drug Discovery·Bryan T HennessyGordon B Mills
Jul 22, 2006·Endocrinology·Yongmei WangDaniel D Bikle
Mar 3, 2007·The European Journal of Neuroscience·Haviryaji S G KalluriRobert J Dempsey
Apr 14, 2007·International Orthopaedics·Aziz AbbaspourNatsuo Yasui
May 1, 2007·Developmental Biology·Guoyan WangFrank Beier

❮ Previous
Next ❯

Citations

Mar 15, 2012·The Journal of Biological Chemistry·Takao KoshimizuToshimi Michigami
Apr 9, 2013·The Journal of Clinical Investigation·L Ashley WatsonNathalie G Bérubé
Nov 10, 2009·Molecular Endocrinology·Michele R HutchisonPerrin C White
Feb 12, 2009·Journal of Cell Science·Aditi Mukherjee, Peter Rotwein
Jan 30, 2010·PloS One·Veronica UliciFrank Beier
Jun 28, 2014·Archives of Oral Biology·Zhennan DengHaiyang Yu
Jun 16, 2014·International Journal of Oral and Maxillofacial Surgery·Z LiZ-B Li
May 4, 2013·Cellular and Molecular Life Sciences : CMLS·Toshimi Michigami
Mar 12, 2010·European Journal of Medical Genetics·Vera UlianaAlessandra Renieri
Oct 6, 2009·Metabolism: Clinical and Experimental·Pan MaHongchen Liu
Mar 31, 2009·Cell Biochemistry and Function·C PassC Farquharson
Mar 13, 2012·Journal of Orthopaedic Research : Official Publication of the Orthopaedic Research Society·Shirine E UsmaniFrank Beier
Jun 1, 2010·Journal of Cellular Biochemistry·Frank Beier, Richard F Loeser
Mar 29, 2014·Birth Defects Research. Part C, Embryo Today : Reviews·Margaret Man-Ger Sun, Frank Beier
Dec 19, 2009·Journal of Cellular Physiology·Jeremy PriceHydar Ali
Dec 4, 2009·The Anatomical Record : Advances in Integrative Anatomy and Evolutionary Biology·Erik Kern HarringtonKathy K H Svoboda
Mar 5, 2010·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Lai WangR Tracy Ballock
May 24, 2014·Osteoarthritis and Cartilage·M M-G Sun, F Beier
Jun 3, 2008·Developmental Biology·Cristina C TeixeiraFrank Beier
Feb 15, 2015·Mechanisms of Ageing and Development·Ping Kwan
Jun 18, 2016·Proceedings of the National Academy of Sciences of the United States of America·Rachel RuoffVictoria Kolupaeva
Dec 14, 2016·PloS One·R Nicole HowieJames J Cray
Feb 2, 2013·The American Journal of Sports Medicine·Hajime UtsunomiyaToshitaka Nakamura
Apr 9, 2014·Molecular and Cellular Biology·Chantal ForristalFrederick A Dick
Dec 5, 2013·The Journal of Biological Chemistry·Meeyoung ParkShmuel Muallem
May 18, 2020·Current Osteoporosis Reports·Holly L Racine, Maria A Serrat

❮ Previous
Next ❯

Methods Mentioned

BETA
PCR

Software Mentioned

Felix32
Openlab
GraphPad Prism

Related Concepts

Related Feeds

Arterial-Venous in Development & Disease

Arterial-venous development may play a crucial role in cardiovascular diseases. Here is the latest research.

Aminoglycosides (ASM)

Aminoglycoside is a medicinal and bacteriologic category of traditional Gram-negative antibacterial medications that inhibit protein synthesis and contain as a portion of the molecule an amino-modified glycoside. Discover the latest research on aminoglycoside here.

Cardiomyopathy

Cardiomyopathy is a disease of the heart muscle, that can lead to muscular or electrical dysfunction of the heart. It is often an irreversible disease that is associated with a poor prognosis. There are different causes and classifications of cardiomyopathies. Here are the latest discoveries pertaining to this disease.

Aminoglycosides

Aminoglycoside is a medicinal and bacteriologic category of traditional Gram-negative antibacterial medications that inhibit protein synthesis and contain as a portion of the molecule an amino-modified glycoside. Discover the latest research on aminoglycoside here.

AKT Pathway

This feed focuses on the AKT serine/threonine kinase, which is an important signaling pathway involved in processes such as glucose metabolism and cell survival.

Calcium & Bioenergetics

Bioenergetic processes, including cellular respiration and photosynthesis, concern the transformation of energy by cells. Here is the latest research on the role of calcium in bioenergetics.

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