Uncoupling of chondrocyte differentiation and perichondrial mineralization underlies the skeletal dysplasia in tricho-rhino-phalangeal syndrome.

Human Molecular Genetics
Dobrawa NapieralaBrendan Lee

Abstract

Tricho-rhino-phalangeal syndrome (TRPS) is an autosomal dominant craniofacial and skeletal dysplasia that is caused by mutations involving the TRPS1 gene. Patients with TRPS have short stature, hip abnormalities, cone-shaped epiphyses and premature closure of growth plates reflecting defects in endochondral ossification. The TRPS1 gene encodes for the transcription factor TRPS1 that has been demonstrated to repress transcription in vitro. To elucidate the molecular mechanisms underlying skeletal abnormalities in TRPS, we analyzed Trps1 mutant mice (Trps1DeltaGT mice). Analyses of growth plates demonstrated delayed chondrocyte differentiation and accelerated mineralization of perichondrium in Trps1 mutant mice. These abnormalities were accompanied by increased Runx2 and Ihh expression and increased Indian hedgehog signaling. We demonstrated that Trps1 physically interacts with Runx2 and represses Runx2-mediated trans-activation. Importantly, generation of Trps1(DeltaGT/+);Runx2(+/-) double heterozygous mice rescued the opposite growth plate phenotypes of single mutants, demonstrating the genetic interaction between Trps1 and Runx2 transcription factors. Collectively, these data suggest that skeletal dysplasia in TRPS is caused b...Continue Reading

References

Apr 1, 1997·Molecular and Cellular Biology·V LefebvreB de Crombrugghe
May 1, 1997·Obstetrics and Gynecology·A M PoutaT J Laatikainen
Mar 18, 2000·The Journal of Biological Chemistry·H EnomotoT Komori
Jul 27, 2000·Journal of Cellular Physiology·H DrissiG S Stein
Nov 21, 2000·Developmental Dynamics : an Official Publication of the American Association of Anatomists·P Ducy
Dec 12, 2000·American Journal of Human Genetics·H J LüdeckeB Horsthemke
May 16, 2003·Nature·Henry M Kronenberg
Oct 1, 2003·Mechanisms of Development·Melanie KunathAndrea Vortkamp
Jun 14, 2005·American Journal of Human Genetics·Qiping ZhengDeborah Krakow
Sep 6, 2005·Molecular Genetics and Metabolism·Dobrawa NapieralaBrendan Lee
Dec 5, 2006·Proceedings of the National Academy of Sciences of the United States of America·Guang ZhouBrendan Lee
Nov 13, 2007·Developmental Biology·Hiroki SuemotoReinhard Fässler

❮ Previous
Next ❯

Citations

Sep 29, 2011·Cell and Tissue Research·Thomas DoetschmanMohamad Azhar
Mar 20, 2012·Cell and Tissue Research·Ikumi MichikamiMakoto Abe
Dec 2, 2009·Pediatric Nephrology : Journal of the International Pediatric Nephrology Association·Manuela Wuelling, Andrea Vortkamp
Jul 16, 2011·Hormones & Cancer·Jie Qing ChenLaszlo Radvanyi
Apr 11, 2013·European Journal of Human Genetics : EJHG·Carole CorsiniDavid Genevieve
May 1, 2012·The Journal of Biological Chemistry·Ying ZhangGary S Stein
Jun 19, 2013·Assay and Drug Development Technologies·Martin BrandtRobert B Kirkpatrick
Sep 22, 2012·Stem Cells and Development·Nadejda V MezentsevaLeonard M Eisenberg
Feb 8, 2011·PloS One·Bettina KellerBrendan Lee
Jul 26, 2011·The Journal of Endocrinology·Colin Farquharson, Katherine Staines
Apr 7, 2010·Connective Tissue Research·Monica PrasadChunlin Qin
Jul 17, 2010·American Journal of Medical Genetics. Part a·Kosuke IzumiDerek E Neilson
Feb 9, 2012·American Journal of Medical Genetics. Part a·Nina PerezaBorut Peterlin
Apr 18, 2012·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Dobrawa NapieralaBrendan Lee
Apr 30, 2013·International Journal of Dermatology·Muhammad FarooqYutaka Shimomura
Jun 10, 2014·The Journal of Dermatology·Tomomi FujisawaMariko Seishima
Mar 29, 2014·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Robert J Hinton
Mar 27, 2016·Gene·Sukru GulluogluOmer Faruk Bayrak
Mar 18, 2015·Molecular Genetics and Metabolism·Shan ChenYangjin Bae
May 22, 2013·Case Reports in Genetics·Catarina DiasJorge Sales Marques
Dec 3, 2010·Experimental and Molecular Pathology·Seiji KannoYasuteru Muragaki
Jun 4, 2016·Genesis : the Journal of Genetics and Development·Ahmed G NomirMakoto Abe
Oct 30, 2016·Seminars in Cell & Developmental Biology·Chia-Feng LiuVéronique Lefebvre
Jan 5, 2017·Cold Spring Harbor Molecular Case Studies·Diane B ZastrowMatthew T Wheeler
Jul 18, 2009·American Journal of Medical Genetics. Part a·Maria PiccioneGiovanni Corsello
Aug 17, 2014·The Journal of Biological Chemistry·Maria KuzynskiDobrawa Napierala
Feb 26, 2019·Nature Medicine·Giedre GrigelionieneTatsuya Kobayashi
Aug 3, 2019·JBMR Plus·Scott DillonColin Farquharson

❮ 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.