Transcription factor Hes1 modulates osteoarthritis development in cooperation with calcium/calmodulin-dependent protein kinase 2

Proceedings of the National Academy of Sciences of the United States of America
Shurei SugitaTaku Saito

Abstract

Notch signaling modulates skeletal formation and pathogenesis of osteoarthritis (OA) through induction of catabolic factors. Here we examined roles of Hes1, a transcription factor and important target of Notch signaling, in these processes. SRY-box containing gene 9 (Sox9)-Cre mice were mated with Hes1(fl/fl) mice to generate tissue-specific deletion of Hes1 from chondroprogenitor cells; this deletion caused no obvious abnormality in the perinatal period. Notably, OA development was suppressed when Hes1 was deleted from articular cartilage after skeletal growth in type II collagen (Col2a1)-Cre(ERT);Hes1(fl/fl) mice. In cultured chondrocytes, Hes1 induced metallopeptidase with thrombospondin type 1 motif, 5 (Adamts5) and matrix metalloproteinase-13 (Mmp13), which are catabolic enzymes that break down cartilage matrix. ChIP-seq and luciferase assays identified Hes1-responsive regions in intronic sites of both genes; the region in the ADAMTS5 gene contained a typical consensus sequence for Hes1 binding, whereas that in the MMP13 gene did not. Additionally, microarray analysis, together with the ChIP-seq, revealed novel Hes1 target genes, including Il6 and Il1rl1, coding a receptor for IL-33. We further identified calcium/calmoduli...Continue Reading

References

Dec 7, 2000·Cytokines, Cellular & Molecular Therapy·S KanekoJ Kagawa
May 16, 2003·Nature·Henry M Kronenberg
Oct 24, 2003·Nature·L M CalviD T Scadden
Apr 1, 2005·Nature·Heather StantonAmanda J Fosang
May 18, 2005·Osteoarthritis and Cartilage·S KamekuraH Kawaguchi
May 27, 2005·Nature Neuroscience·Keejung Yoon, Nicholas Gaiano
Oct 6, 2005·Proceedings of the National Academy of Sciences of the United States of America·Haruhiko AkiyamaBenoit de Crombrugghe
Oct 26, 2005·Osteoarthritis and Cartilage·K P H PritzkerW B van den Berg
Nov 1, 2006·Nature Clinical Practice. Rheumatology·Norihiro Nishimoto, Tadamitsu Kishimoto
Mar 3, 2007·Development·Ryoichiro KageyamaTaeko Kobayashi
May 4, 2007·Scandinavian Journal of Rheumatology·F DossB Müller
Aug 21, 2008·Nature Protocols·Marjolaine GossetClaire Jacques
Sep 19, 2008·Genome Biology·Yong ZhangX Shirley Liu
Feb 5, 2009·Autoimmunity Reviews·J E FonsecaE Choy
Oct 27, 2009·Rheumatology·Jean-Michel Dayer, Ernest Choy
Sep 8, 2010·Current Topics in Developmental Biology·Brendan D'SouzaGerry Weinmaster
Mar 7, 2012·Immunologic Research·Marija MilovanovicMiodrag L Lukic
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 16, 2013·Proceedings of the National Academy of Sciences of the United States of America·Yoko HosakaHiroshi Kawaguchi
Apr 5, 2013·Journal of Investigative Medicine : the Official Publication of the American Federation for Clinical Research·Xiao-lin LiJing Lu
May 2, 2013·Current Opinion in Structural Biology·Margaret M StrattonJohn Kuriyan
Jun 27, 2013·Human Immunology·Wang-Dong XuDong-Qing Ye
Nov 21, 2013·Annals of the Rheumatic Diseases·Jong-Sung ParkDong-Gyu Jo
Nov 26, 2013·Nucleic Acids Research·Donna KarolchikW James Kent

❮ Previous
Next ❯

Citations

Jan 20, 2016·Nature Immunology·Nikolas T Martin, Michael U Martin
Aug 19, 2015·Frontiers in Cellular Neuroscience·Cedric Boeckx, Antonio Benítez-Burraco
Jul 23, 2015·Science Signaling·Anusha Ratneswaran, Frank Beier
Oct 30, 2016·Arthritis & Rheumatology·Yuki TaniguchiTaku Saito
Mar 3, 2018·International Journal of Molecular Sciences·Ju-Ryoung KimHyun Ah Kim
Jan 9, 2018·Histochemistry and Cell Biology·Riko NishimuraYoshifumi Takahata
Nov 1, 2016·Annals of the Rheumatic Diseases·Augustin LatourtePascal Richette
Dec 17, 2017·Immunological Reviews·Diana BoraschiMichael U Martin
Mar 5, 2019·F1000Research·David A YoungDavid J Wilkinson
Apr 14, 2016·Endocrine Reviews·Stefano Zanotti, Ernesto Canalis
Aug 20, 2019·Cell Communication and Signaling : CCS·Yudan WangFaming Tian
May 17, 2017·Arthritis Research & Therapy·Taku Saito, Sakae Tanaka
Sep 27, 2016·The Journal of Veterinary Medical Science·Wuyun DalaiKeiichi Saeki
Sep 29, 2017·Journal of Bone Metabolism·Riko NishimuraHiroko Yagi
Oct 21, 2016·The Journal of Biological Chemistry·Yoshiaki SuzukiYuji Imaizumi
Aug 9, 2018·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Ruzanna ShkhyanDenis Evseenko
Feb 13, 2021·International Journal of Molecular Sciences·Qichan Hu, Melanie Ecker
Mar 13, 2021·Scientific Reports·Giovanna NalessoFrancesco Dell'Accio
Aug 27, 2021·Frontiers in Molecular Biosciences·Lejian JiangMao Lin
Nov 10, 2021·Journal of Bone and Mineral Metabolism·Taizo KanekoTaku Saito

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.