Notch signaling through Jagged-1 is necessary to initiate chondrogenesis in human bone marrow stromal cells but must be switched off to complete chondrogenesis

Stem Cells
Rachel A OldershawTimothy E Hardingham

Abstract

We investigated Notch signaling during chondrogenesis in human bone marrow stromal cells (hMSC) in three-dimensional cell aggregate culture. Expression analysis of Notch pathway genes in 14-day chondrogenic cultures showed that the Notch ligand Jagged-1 (Jag-1) sharply increased in expression, peaking at day 2, and then declined. A Notch target gene, HEY-1, was also expressed, with a temporal profile that closely followed the expression of Jag-1, and this preceded the rise in type II collagen expression that characterized chondrogenesis. We demonstrated that the shut-down in Notch signaling was critical for full chondrogenesis, as adenoviral human Jag-1 transduction of hMSC, which caused continuous elevated expression of Jag-1 and sustained Notch signaling over 14 days, completely blocked chondrogenesis. In these cultures, there was inhibited production of extracellular matrix, and the gene expression of aggrecan and type II collagen were strongly suppressed; this may reflect the retention of a prechondrogenic state. The JAG-1-mediated Notch signaling was also shown to be necessary for chondrogenesis, as N-[N-(3,5-difluorophenacetyl-L-alanyl)]-(S)-phenylglycine t-butyl ester (DAPT) added to cultures on days 0-14 or just days 0-...Continue Reading

References

Jun 1, 1992·Clinical Biochemistry·K E Kuettner
Sep 1, 1991·Journal of Orthopaedic Research : Official Publication of the Orthopaedic Research Society·A I Caplan
Sep 28, 1995·Nature·S JarriaultA Israel
Mar 1, 1997·Journal of Virology·S HardyM L Phipps
Jun 1, 1997·Nature Genetics·D M BellK S Cheah
May 15, 1997·Microscopy Research and Technique·E B HunzikerD Studer
Feb 11, 1998·Experimental Cell Research·B JohnstoneJ U Yoo
Jan 5, 1999·Science·H QiS Artavanis-Tsakonas
Jan 23, 1999·Tissue Engineering·A M MackayM F Pittenger
Mar 13, 1999·Seminars in Cell & Developmental Biology·A Joutel, E Tournier-Lasserve
Apr 2, 1999·Science·M F PittengerD R Marshak
Apr 30, 1999·Science·S Artavanis-TsakonasR J Lake
May 13, 1999·Nature Genetics·W BiB de Crombrugghe
Dec 11, 1999·Current Opinion in Pediatrics·I D KrantzN B Spinner
Aug 29, 2000·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·C CrosnierM Vekemans
Sep 1, 2000·Osteoarthritis and Cartilage·A M DeLiseR S Tuan
Sep 9, 2000·Journal of Medical Genetics·E A JonesD I Wilson
Nov 30, 2000·Proceedings of the National Academy of Sciences of the United States of America·O NakagawaE N Olson
Jan 9, 2001·Journal of Neurochemistry·H F DoveyJ E Audia
Apr 9, 2001·Seminars in Cell & Developmental Biology·C B Knudson, W Knudson
May 26, 2001·The Journal of Endocrinology·I SekiyaM Noda
Oct 30, 2001·Osteoarthritis and Cartilage·M MastrogiacomoR Quarto
Oct 30, 2001·Osteoarthritis and Cartilage·V LefebvreB de Crombrugghe
Feb 16, 2002·Methods : a Companion to Methods in Enzymology·K J Livak, T D Schmittgen
May 10, 2002·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Keith Brennan, Philip Gardner
Aug 30, 2002·Current Opinion in Genetics & Development·Alfonso Martinez AriasKeith Brennan
Sep 24, 2002·American Journal of Medical Genetics·Ian D Krantz
Sep 24, 2002·American Journal of Medical Genetics·Binita M KamathIan D Krantz
Sep 24, 2002·American Journal of Medical Genetics·Binita M KamathIan D Krantz
Oct 26, 2002·The Journal of Biological Chemistry·Ping ZhangDavid G Stokes
Jan 28, 2003·Journal of Cellular Physiology·Tatsuya IsoYasuo Hamamori
Apr 30, 2003·Arthritis Research & Therapy·Rocky S TuanRichard Tuli
Jul 25, 2003·Experimental Cell Research·Satoshi GojoAkihiro Umezawa

❮ Previous
Next ❯

Citations

Mar 27, 2009·Breast Cancer Research and Treatment·Patrick MüllerAnders Ström
Dec 10, 2009·In Vitro Cellular & Developmental Biology. Animal·Lisa ShawSusan J Kimber
Aug 27, 2011·Cell Death and Differentiation·R HallerJ Rohwedel
Oct 23, 2010·Nature Biotechnology·Rachel A OldershawSusan J Kimber
Mar 5, 2011·Stem Cell Research & Therapy·Janice O'SullivanCynthia M Coleman
Apr 19, 2008·Endocrinology·Stefano ZanottiErnesto Canalis
Mar 29, 2011·European Journal of Medical Genetics·Veronica BertiniPaolo Simi
Sep 4, 2012·Journal of Genetics·Behnaz BakhshandehNasser Ghaemi
May 21, 2013·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Simin LuoShangyun Sun
Jan 19, 2010·Biochemical and Biophysical Research Communications·Wei JingWeidong Tian
Nov 3, 2015·Matrix Biology : Journal of the International Society for Matrix Biology·Alan D MurdochRussell J Fernandes
Jun 6, 2009·Journal of Anatomy·Rebecca WilliamsCharles W Archer
Aug 6, 2011·Journal of Orthopaedic Research : Official Publication of the Orthopaedic Research Society·Michael I DishowitzKurt D Hankenson
Jul 29, 2010·Journal of Orthopaedic Research : Official Publication of the Orthopaedic Research Society·John D KisidayDavid D Frisbie
Oct 19, 2012·International Journal of Experimental Pathology·Rachel A Oldershaw
Mar 2, 2012·Journal of Cellular Physiology·Nalinkanth V Ghone, Warren L Grayson
Jun 19, 2013·Journal of Biomedical Materials Research. Part a·Michael I DishowitzKurt D Hankenson
Dec 31, 2009·Journal of Oral Pathology & Medicine : Official Publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology·Tong-Han ZhangGuang-Sen Zheng
Jul 23, 2013·Journal of Tissue Engineering and Regenerative Medicine·Anna T BriniRoberta Piva
Jun 13, 2009·Bone·Feyza Engin, Brendan Lee
May 2, 2009·Bone·Rachel A Oldershaw, Tim E Hardingham
Dec 21, 2010·Archives of Oral Biology·Maria J SerranoRobert J Hinton
Jul 17, 2016·Seminars in Cell & Developmental Biology·Diego Correa, Steven A Lietman
Sep 15, 2016·Stem Cell Research & Therapy·Mandy J PeffersPeter D Clegg
Oct 7, 2017·Tissue Engineering. Part a·Troy D BornesNadr M Jomha
May 6, 2019·Cellular and Molecular Life Sciences : CMLS·Abderrahim NajiNarufumi Suganuma
Mar 16, 2011·Alternatives to Laboratory Animals : ATLA·Tim Hardingham
Jul 17, 2012·Clinical Orthopaedics and Related Research·Umut Atakan GurkanOzan Akkus
Feb 27, 2020·International Journal of Molecular Sciences·Maurizio Mangolini, Ingo Ringshausen
Feb 26, 2019·Stem Cells and Development·Rachel OldershawAnnette Meeson
Nov 11, 2020·Journal of Tissue Engineering and Regenerative Medicine·Masato KobayashiNorimasa Nakamura
May 21, 2021·IScience·Jerome Nicolas JanssenNicolai Miosge

❮ Previous
Next ❯

Related Concepts

Related Feeds

Alagille Syndrome

Alagille syndrome is a multi-system genetic disorder that can affect the liver, heart, and other parts of the body. It’s characterization includes heart problems, liver damage, jaundice, and xanthomas. Here is the latest research.

Allogenic & Autologous Therapies

Allogenic therapies are generated in large batches from unrelated donor tissues such as bone marrow. In contrast, autologous therapies are manufactures as a single lot from the patient being treated. Here is the latest research on allogenic and autologous therapies.