GREM1 Is a Key Regulator of Synoviocyte Hyperplasia and Invasiveness

The Journal of Rheumatology
Eun-Jin HanWan-Uk Kim

Abstract

To investigate the expression of Gremlin 1 (GREM1), an antagonist of bone morphogenetic protein, in rheumatoid arthritis (RA) synovia and its involvement in the hyperplasia and invasiveness of fibroblast-like synoviocytes of RA (RA-FLS). Computational analysis was introduced to identify FLS-predominant regulators. GREM1 expression was examined by immunohistochemistry, real-time PCR, and ELISA. FLS proliferation and apoptosis were determined using tetrazolium-based colorimetric assay and APOPercentage assay, respectively. FLS migration and invasion were evaluated by wound migration and Matrigel invasion assay, respectively. Expressions of Bax, Bcl2, pErk1/2, and pAkt were detected by Western blot analysis. Through global transcriptome profiling, we identified a GREM1 gene predominantly expressed in RA-FLS. Indeed, the GREM1 expression was higher in synovia, synovial fluids, and FLS of patients with RA than in those of patients with osteoarthritis, and its levels correlated well with proinflammatory cytokine concentrations. Knockdown of GREM1 transcripts using short interfering RNA (siRNA) reduced the proliferation and survival of RA-FLS along with downregulation of pErk1/2, pAkt, and Bcl2 expressions, whereas it induced Bax expr...Continue Reading

References

Aug 1, 1996·Current Opinion in Genetics & Development·B L Hogan
Oct 27, 1997·Arthritis and Rheumatism·A RoivainenP Toivanen
Mar 18, 2000·The Journal of Biological Chemistry·L Z TopolD G Blair
Dec 26, 2001·Nucleic Acids Research·Ron EdgarAlex E Lash
Apr 18, 2003·Endocrine Reviews·Ernesto CanalisElisabetta Gazzerro
Jan 7, 2004·Genome Research·Eitan E WinterChris P Ponting
Sep 24, 2004·Arthritis Research & Therapy·Hoang Tu-RappSaleh M Ibrahim
Oct 16, 2004·Proceedings of the National Academy of Sciences of the United States of America·Hisashi HaradaStanley J Korsmeyer
Nov 23, 2005·Proceedings of the National Academy of Sciences of the United States of America·Daehee HwangHamid Bolouri
Sep 28, 2006·Proceedings of the National Academy of Sciences of the United States of America·Julie B SneddonPatrick O Brown
Oct 4, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Mi-Sook LeeSung Ho Ryu
Oct 4, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Wan-Uk KimChul-Soo Cho
Jan 27, 2007·Science·David M LeeMichael B Brenner
Mar 7, 2007·Molecular Cancer Therapeutics·Uma T ShankavaramJohn N Weinstein
May 26, 2007·Nature Reviews. Immunology·Iain B McInnes, Georg Schett
Dec 24, 2008·Proceedings of the National Academy of Sciences of the United States of America·Kasper LageSøren Brunak
Apr 8, 2009·Genome Medicine·Charles AuffrayLeroy Hood
Dec 23, 2009·International Journal of Cancer. Journal International Du Cancer·Chandramu ChettyJasti S Rao
Jan 15, 2010·The Journal of Biological Chemistry·He-Jin LeeSeung-Jae Lee
Mar 3, 2010·Immunological Reviews·Beatrix Bartok, Gary S Firestein
Mar 9, 2010·Nature Methods·Shai S Shen-OrrAtul J Butte
Jul 28, 2010·Blood·Stefania MitolaMarco Presta
Dec 14, 2011·The New England Journal of Medicine·Iain B McInnes, Georg Schett
May 26, 2012·Journal of Cellular Biochemistry·Sharon L HyzyBarbara D Boyan
Oct 12, 2012·Angiogenesis·Cosetta RavelliMarco Presta
Nov 14, 2012·Nature Reviews. Rheumatology·Nunzio Bottini, Gary S Firestein
Nov 13, 2013·Nature Reviews. Rheumatology·Gerd R BurmesterThomas Dörner

❮ Previous
Next ❯

Citations

Apr 30, 2017·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Qian LiZhiming Hao
Dec 5, 2018·Journal of Periodontal Research·Mandeep S GhumanFrancis J Hughes
Mar 6, 2018·BMC Genomics·Elena A PudovaAnastasiya V Snezhkina
Oct 13, 2019·The Journal of Biological Chemistry·Louise R DuttonDerek P Brazil
Sep 29, 2019·Biomolecules·Cristina Sánchez-de-DiegoFrancesc Ventura
Aug 4, 2021·Bone & Joint Research·Mengmeng DuanJing Xie

❮ Previous
Next ❯

Related Concepts

Related Feeds

BCL-2 Family Proteins

BLC-2 family proteins are a group that share the same homologous BH domain. They play many different roles including pro-survival signals, mitochondria-mediated apoptosis and removal or damaged cells. They are often regulated by phosphorylation, affecting their catalytic activity. Here is the latest research on BCL-2 family proteins.

Cell Migration

Cell migration is involved in a variety of physiological and pathological processes such as embryonic development, cancer metastasis, blood vessel formation and remoulding, tissue regeneration, immune surveillance and inflammation. Here is the latest research.

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

Adhesion Molecules in Health and Disease

Cell adhesion molecules are a subset of cell adhesion proteins located on the cell surface involved in binding with other cells or with the extracellular matrix in the process called cell adhesion. In essence, cell adhesion molecules help cells stick to each other and to their surroundings. Cell adhesion is a crucial component in maintaining tissue structure and function. Discover the latest research on adhesion molecule and their role in health and disease here.