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

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  • NYC Bone Seminar 03/20/03 NICOLA PARTRIDGE on PARATHYROID HORMONEREGULATION OF GENE EXPRESSION IN THE OSTEOBLAST

    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.

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    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).

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    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.

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    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
    *************************************

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