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academies
Cell Science, Stem Cell Research &
Pharmacological Regenerative Medicine
November 29-30, 2017 | Atlanta, USA
Annual Congress on
Adv cel sci tissue cul 2017 | Volume 1 Issue 2
Prostaglandin E2 receptor (EP2): A novel target to attenuate inflammation and excessive bone loss
during autoimmune arthritis
Rangaiah Shashidharamurthy
Philadelphia College of Osteopathic Medicine, USA
P
rostaglandin-E2 receptors (subtype EP2) are known to
be activated during various autoimmune inflammatory
disorders including rheumatoid arthritis (RA) and play an
essential role in exacerbating the bone damage during RA.
Herein, we have shown that EP2 antagonism attenuates
the ongoing inflammation and excessive bone loss in
collagen-induced arthritis model. Further, EP2 antagonists
significantly down-regulated the serum pro-inflammatory
cytokine response compared to untreated arthritic mice. We
have also investigated the anti-osteoclastogenic activity of
EP2 antagonists using an
in vitro
osteoclastogenesis model
using mouse monocytic cell line. We observed significantly
increased size and number of osteoclasts by both PGE2 and
butaprost (selective EP2 agonist) compared to receptor
activator of nuclear factor kappa-B ligand (RANKL) alone
treated cells. We did not observe significant difference
in number of osteoclasts between PGE2 and butaprost.
In addition, 10µM concentration of various EP2 specific
antagonists inhibited RANKL-induced osteoclast formation.
Western blot analysis revealed that EP2 antagonists
decreased the expression of c-Fos but not NFATc1 and NFkB,
which are the master regulators of osteoclastogenesis.
These data indicates the direct effect of EP2 antagonists
on going inflammation and bone cells in preventing the
severe bone damage implying EP2 receptors play a major
role during osteoclast formation. Therefore, EP2 receptors
should be explored as a therapeutic target to blunt the
ongoing inflammation as well as excessive bone loss during
autoimmune arthritis.
Speaker Biography
Rangaiah Shashidharamurthy is Associate Professor of Department of Pharmaceutical
Sciences, PCOM-School of Pharmacy, Georgia campus. He has published more than
38 papers in peer reviewed journals and also serving as an external reviewer and
editorial board member for many of the international peer reviewed journals. Dr.
Shashidharamurthy research interest is in investigating the pathogenesis of chronic
autoimmune/inflammatory disorders such as vasculitis and arthritis.
e:
rangaiahsh@pcom.edu