PDA

View Full Version : NYC Bone Seminar 03/20/03 NICOLA PARTRIDGE on PARATHYROID HORMONEREGULATION OF GENE EXPRESSION IN THE OSTEOBLAST



Steve Cowin
03-14-2003, 12:57 AM
To Bone Researchers in the NYC area:
The NYC Mineralized Tissue Seminar will have its first spring
seminar on Thursday night March 20th in room C201 at the CUNY
Graduate Center at 7 PM. The speaker is NICOLA PARTRIDGE,
UMDNJ-Robert Wood Johnson Medical School. She will speak on
PARATHYROID HORMONE REGULATION OF GENE EXPRESSION IN THE OSTEOBLAST.
An abstract for the seminar is below.
The Bone Seminar Series has as its focus the mechanosensory system in
bone. The series sponsors eight seminars a year beginning in
September and continuing until April or May. The seminar program is
regularly posted on www.bonenet.net, a website dedicated to research
on the mechanosensory system in bone.

XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX

THE SPRING 2003 BONE SEMINAR PROGRAM

The first three seminar series will be held in Room C201 (on the
concourse level, below the ground floor) at the CUNY Graduate Center
on Thursdays from 7 to 8:30 PM. The fourth seminar on June 5th will
be held in Room 9204. The CUNY Graduate Center is in the Altman
Building at the corner of 34th Street and 5th Avenue, catty-corner
from the Empire State Building. There will be some socializing before
the seminar in the seminar room from 5:45 PM. Also, from 5:45 PM
until 7 PM there will be food (fruit plate, vegetable plate, cookies)
and drink (coffee and soft drinks) available in the seminar room.
There is also a Graduate Center snack bar on the first floor; besides
the usual snacks and drinks the 365 Express also carries beer and
wine.
There are several subway lines nearby and it is less than a
ten-minute walk to either Grand Central Station or Penn Station.
There is money to support parking for graduate students, apply to
Steve Cowin (contact information at the bottom).

XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX

MARCH 20th, 2003 in room C201 at the CUNY Graduate Center at 7 PM.

Speaker: NICOLA C. PARTRIDGE, Ph.D., Professor and Chairman,
Department of Physiology & Biophysics, UMDNJ-Robert Wood Johnson
Medical School, Piscataway, NJ 08854.

Title: PARATHYROID HORMONE REGULATION OF GENE EXPRESSION IN THE OSTEOBLAST

Abstract: Parathyroid hormone (PTH) plays a central role in
regulation of calcium metabolism but also appears to have a role as
an anabolic hormone for bone. The hormone has multiple actions,
including many direct changes in the functions of the osteoblast. To
date, all of its skeletal effects appear to be mediated by binding to
a single receptor on osteoblasts. In this process, PTH causes a
change in osteoblastic gene expression and function. Apart from
producing osteoclast-activating factors such as RANKL and interleukin
-6 (IL-6) in response to PTH, the osteoblast appears to also have a
direct role in matrix degradation in response to this hormone. For
instance, PTH induces collagenase-3 gene transcription in
osteoblastic cells through a cAMP-dependent pathway requiring de novo
protein synthesis. Thus, this is a secondary effect that involves the
induction and activation of specific transcription factors acting on
this gene. We identified the PTH-response elements as being the
activator protein-1 (AP-1) and the core binding factor a1 (Cbfa1)
binding sites in the collagenase-3 promoter. We have demonstrated a
PTH-dependent cooperative interaction between the sites and the
proteins binding to them. By gel shift analysis, we have shown
enhanced binding of c-Fos and c-Jun proteins at the AP-1 site upon
treatment with PTH but no significant change in the level of Cbfa1
binding to its site. Supporting our earlier work, the PKA pathway was
shown to be the only pathway regulating the collagenase-3 promoter as
a mediator of PTH action. The importance of this pathway was
demonstrated by the fact that PTH stimulates the transactivation of
activation domain-3 in Cbfa1 through its PKA site. PTH regulates both
transcription factors through this pathway, either by increasing
their expression or altering their phosphorylation. Our hypothesis of
the functions of these proteins is that they interact physically in a
nucleosomal structure, recruiting other proteins such as
co-activators, modifiers of the nucleosome and the general
transcription factors. If there is time, I will talk about some of
our new work on PTH regulation of novel genes in osteoblasts.

RESEARCH INTERESTS OF NICOLA PARTRIDGE: We have shown that
parathyroid hormone (PTH) induces the transcription of collagenase-3
in osteoblastic cells. This involves the protein kinase A pathway
and induction of activator protein-1 transcription factors as well as
phosphorylation of another transcription factor, core binding factor
a1. Thus, PTH regulates both transcription factors through this
pathway, either by increasing their expression or altering their
phosphorylation. Our hypothesis of the functions of these proteins is
that they interact physically in a nucleosomal structure, recruiting
other proteins such as co-activators, modifiers of the nucleosome and
the general transcription factors. In another project, we are
investigating the signal transduction pathways whereby PTH induces
anabolic effects on bone and determining novel genes regulated by
this hormone. In two other projects we have shown that extracellular
concentrations of collagenase-3 are regulated by the existence of a
specific receptor that binds the enzyme. Subsequent internalization
and degradation of collagenase-3 require transfer to the endocytotic
receptor, the low-density lipoprotein receptor-related protein. We
have recently purified and identified the specific receptor as a
170-kDa protein. We are now further characterizing the collagenase-3
removal process in osteoblasts, fibroblasts as well as chondrocytes
from patients with osteoarthritis. The latter work could lead to new
treatments for this disease.

XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX

ORGANIZATION OF THE SEMINAR SERIES

The Interinstitutional Steering Committee (ISC) will make decisions
concerning the seminar series, including the selection of speakers.
Interesting, high quality seminar speakers are sought. Seminar
attendees are asked to help in the identification of investigators
with new results relative to the bone research, questions of current
interest and distinguished bone researchers visiting New York City
who might be persuaded to present a seminar. Presentations by
advanced graduate students and post-docs are encouraged.
The members of the Interinstitutional Steering Committee (ISC) are
Adele Boskey (Head of the Mineralized Tissue Section at the Hospital
for Special Surgery and Professor of Biochemistry at the Weill
Medical College of Cornell University), Timothy Bromage (Director of
the Hard Tissue Research Unit and Professor of Anthropology at Hunter
College of CUNY), Stephen C. Cowin (Director of the New York Center
for Biomedical Engineering (NYCBE) and Professor of Biomedical and
Mechanical Engineering at the City College of the City University of
New York (CUNY)), Susannah P. Fritton (Director of the Tissue
Mechanics Laboratory, New York Center for Biomedical Engineering and
Associate Professor of Biomedical Engineering at the City College of
CUNY), X. Edward Guo (Director of the Bone Bioengineering Laboratory
and Assistant Professor of Bioengineering at Columbia University),
Clinton T. Rubin (Professor and Chair of the Department of Biomedical
Engineering, and Director of the Center for Advanced Technology in
Medical Biotechnology at SUNY Stony Brook) and Mitchell B. Schaffler
(Director of Orthopaedic Research and Professor of Orthopedics, Cell
Biology and Anatomy at the Mount Sinai School of Medicine). Each of
these people represents a community consisting of senior bone
research people, graduate students and, in most cases, undergraduate
students.

PLEASE DIRECT YOUR QUESTIONS AND FEEDBACK TO

Stephen C. Cowin
Director, New York Center for Biomedical Engineering
School of Engineering
The City College
138th Street and Convent Avenue
New York, NY 10031-9198, U. S. A.

Phone (212) 799-7970 (Office at Home)
Fax (212) 799-7970 (Office at Home)
Phone (212) 650-5208 (Work)
Email

--

************************************
For bone research information, visit .
************************************
PREFERRED MAILING ADDRESS
Stephen C. Cowin
2166 Broadway
Apartment 12D
New York, NY 10024

Phone (212) 799-7970 (Office at Home)
Fax (212) 799-7970 (Office at Home)
Phone (212) 650-5208 (Work)
Fax (212) 650-6727 (Work)
Email

WORK ADDRESS:
Stephen C. Cowin
Director, New York Center for Biomedical Engineering
School of Engineering
The City College
138th Street and Convent Avenue
New York, NY 10031-9198, U. S. A.
*************************************
For information about the New York Center for Biomedical
Engineering visit
*************************************

---------------------------------------------------------------
To unsubscribe send SIGNOFF BIOMCH-L to LISTSERV@nic.surfnet.nl
For information and archives: http://isb.ri.ccf.org/biomch-l
---------------------------------------------------------------