Journal
3 BIOTECH
Volume 11, Issue 12, Pages -Publisher
SPRINGER HEIDELBERG
DOI: 10.1007/s13205-021-03052-8
Keywords
Rheumatoid arthritis; Osteoclasts; Purinergic signaling; ROS; Synoviocytes; TRAP activity
Categories
Funding
- Department of Biosciences, SSSIHL, Prasanthi Nilayam, Anantapur, India
- University Grants Commission, Basic Scientific Research, New Delhi, India [F.4-1/2006 (BSR)/7-164/2007 (BSR)]
- Department of Biotechnology (DBT) Project, New Delhi, India [BT/PR8226/BRB/10/1224/2013]
- Department of Science and Technology (DST), New Delhi, India [EMR/2017/005381]
- Department of Science and Technology (DST)-FIST, New Delhi, India [SR/FST/LSI-616/2014]
- Department of Biotechnology - Bioinformatics (DBT-BIF) Facility, New Delhi, India [BT/BI/25/063/2012]
- University Grants Commission (UGC) - special assistance program (SAP), New Delhi, India [UGC-SAP III: F.3-19/2018/DRS-III(SAP-II)]
- Corning India, Gurugram, Haryana, India
Ask authors/readers for more resources
P2 receptors, activated by nucleotides, play a role in inflammation, cell proliferation, and differentiation, with potential therapeutic implications in rheumatoid arthritis. Experimental evidence suggests that nucleotides can modulate synoviocyte proliferation and macrophage differentiation into osteoclast, highlighting their importance in RA.
P2 receptors are nucleotide-activated receptors involved in inflammation, cell proliferation osteoblastogenesis, osteoclastogenesis and their function. They can be potential role players in the pathophysiology of rheumatoid arthritis (RA). Our analysis of gene expression datasets of synovial tissue biopsy from the GEO database shows changes in the expression levels of P2 receptors. HIG-82, a synovial fibroblast cell line and RAW 264.7, a macrophage cell line are good in vitro models to study RA. Nucleotide addition experiments showed UDP Glucose significantly increased the proliferation of synovial fibroblasts (HIG-82). Similarly, nucleotides such as Adenosine tri-phosphate (ATP), Adenosine di-phosphate (ADP), Uridine tri-phosphate (UTP), Uridine di-phosphate (UDP) and Uridine diphosphoglucose (UDPG) induced elevated reactive oxygen species (ROS) and tartrate Resistant Acid Phosphatase (TRAP) activity in RAW264.7 cells. The ADP-induced TRAP could be inhibited by clopidogrel a P2Y(12) inhibitor. ATP, ADP, UTP, UDP and UDPG also induced osteoclastogenesis as evident from fused multinucleate cells and expression of osteoclast markers (TRAP, Cathepsin K [CTSK]) as determined by Q-PCR. Apyrase (APY) a nucleotidase and an enzyme that is used to modulate extracellular nucleotide concentration is sufficient to induce osteoclastogenesis. Taken together our results show that nucleotides modulate synoviocyte proliferation and macrophage differentiation into osteoclast and play an important role in RA. Nucleotide receptors might be potential therapeutic targets in RA.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available