View Full Version : The Fall 2004 NYC Bone Seminar Series

Steve Cowin
09-13-2004, 11:09 PM
Dear colleagues and students:

The Fall 2004 Bone Seminar Series kicks off Tuesday September 28 with
a presentation by David T. Denhardt PhD of Rutgers University, who
will speak on "Osteopontin, a Cytokine and Bone Matrix Protein,
Augments Bone Remodeling, Metastasis, and Autoimmune Disease

Details of all seminars appear below as well as on our website:


The contents of the rest of this email is as follows:
[1] Bone Seminar Series: General Information
[2] September 28, 2004 Seminar: David T. Denhardt PhD
[3] October 26, 2004 Seminar: Timothy G. Bromage PhD
[4] November 16, 2004: Janet Rubin MD
[5] December 7, 2004: Peter Bullough MD
[6] "Pinch Hitter": Luis Cardoso Landa PhD
[7] Questions and Feedback Contact


[1] Bone Seminar Series: General Information

The Bone Seminar Series focuses on bone research in general and the
study of the mechanosensory system in bone in particular. The Series
consists of eight seminars per academic year, four each in the Fall
and Spring series.

Program information for the Bone Seminars and the annual Bone Fluid
Flow Workshop is regularly posted on our website:


Comments on the website are welcome and may be addressed to Bill
Green at webmaster@bonenet.net or to me Steven Cowin PhD at

Seminars are held in rooms on the ninth floor of the CUNY Graduate
Center on Tuesdays from 7:00 to 8:30 PM. 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. A social hour precedes
each seminar starting at 5:45 PM with food (fruit plate, vegetable
plate, cookies) and drinks (coffee and soft drinks). There is also a
snack bar on the first floor. 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 end of this


[2] September 28, 2004 Seminar

SPEAKER: David T. Denhardt PhD, Department of Cell Biology and
Neuroscience, Rutgers University, Piscataway Campus

TOPIC: Osteopontin, a Cytokine and Bone Matrix Protein, Augments Bone
Remodeling, Metastasis, and Autoimmune Disease Progression

PLACE AND TIME: Room 9204, CUNY Graduate Center, 7:00 PM

ABSTRACT: Osteopontin (OPN) is a phosphorylated, glycosylated protein
found not only extracellularly in all body fluids and in mineralized
matrices but also intracellularly at the cytoskeletal/plasma membrane
interface. The extracellular form is capable of engaging some
half-dozen integrins and at least two CD44 variants. OPN signaling
regulates gene expression (e.g., iNOS expression induced by
endotoxin) and cell motility, stimulating a chemotactic response. It
enhances the survival of cells exposed to various stresses by
inhibiting apoptosis. OPN can stimulate tumor cell metastasis and the
progression of autoimmune disease: Mice lacking OPN are less
susceptible to arthritis induced by anti-type II collagen antibodies
(Noda) and to experimental autoimmune encephalomyelitis induced by
myelin oligodendrocyte glycoprotein peptides (Steinman, Cantor). They
are also unable to remodel bone in response to various stresses
(ovariectomy, hind-limb suspension), possibly in part because OPN is
required for normal osteoclast function (Hruska, Noda, Sodek).

RESEARCH INTERESTS of Dave Denhardt: His research interests currently
focus on the systems physiology of OPN and TIMP-1 (tissue inhibitor
of metalloproteinases-1). Both in different ways stimulate tumor cell
metastasis and he would like to know why. With respect to OPN, he
would like to understand how it functions in such apparently diverse
processes as bone remodeling and autoimmune disease.


[3] October 26, 2004 Seminar

SPEAKER Timothy G. Bromage, PhD, Department of Biomaterials and
Biomimetics, New York University College of Dentistry

Confocal Circularly Polarized Light Microscopy of the Early Hominid Skeleton

PLACE AND TIME: Room 9207, CUNY Graduate Center, 7:00 PM

ABSTRACT: Skeletal microanatomy is typically investigated by some
form of light microscopy on specially prepared samples, such as
histological thin sections, or by scanning electron microscopy (SEM)
of bulk specimens. However, unique African early hominid remains from
Pliocene localities some 2-4 million years old are not readily
available for histological sectioning, and bulk examination by SEM is
restricted to first surfaces. A practical alternative is confocal
scanning optical microscopy (CSOM). This permits "optical sectioning"
upon and below the intact surfaces of opaque materials, which
generates excellent reflection images and provides basic details of
bone and tooth histological microanatomy equal to that produced by
conventional research microscopes.

This is all very well, but African early hominid repositories do not
have available CSOM technologies, requiring that we bring such an
instrument to the fossils. This has prompted development of the first
portable CSOM, the prototype of which has recently been taken to
Ethiopia, Kenya, and South Africa for its first glimpse of the hard
tissue microanatomy of Australopithecus, Paranthropus, and early Homo
species. CSOM imaging of the dentition is demonstrating
species-specific variations of enamel structure related to functional
and life history adaptations. Further, because the portable CSOM is
configured to generate reflected circularly polarized light images,
we are able to study and analyze preferential collagen fiber
orientations in bone tissue and thus skeletal function in our fossil

RESEARCH INTERESTS of Tim Bromage: Comparative hard tissue biology
and microanatomy in relation to functional, life history, and
environmental reconstruction; human evolution; development of
practical solutions to technical problems of mineralized tissue
specimen preparation and imaging.


[4] November 16, 2004 Seminar

SPEAKER: Janet Rubin MD, Professor of Medicine, Division of
Endocrinology and Metabolism, Emory University School of Medicine and
the Atlanta Veterans Affairs Medical Center, Atlanta, GA

TOPIC: Turning Mechanical Signals into Biological Effects

PLACE AND TIME: Room 9205, CUNY Graduate Center, 7:00 PM

ABSTRACT: Biophysical input generated during normal physiologic
loading is a major determinant of bone mass and morphology. Our
laboratory's interest is in how bone cells sense and transduce
signals generated during loading and how this cellular response leads
to skeletal adaptation to its mechanical environment. We have shown
that substrate strain regulates gene expression in bone stromal
cells, decreasing expression of RANKL and increasing expression of
eNOS/nitric oxide. These changes generate a local environment that is
inhibitory for osteoclast recruitment. The ability of mechanical
strain to induce this functional response requires activation of the
ERK1/2 MAP-kinase pathway. The proximal signaling cascade leading to
ERK1/2 activation is stunningly specific, and suggests that the
putative mechanotransducer occupies a discrete membrane location. Our
most recent work suggests that the mechanical signal arises from
events occurring within a lipid raft. Distal to ERK1/2 activation, we
will also consider possible mechanisms by which strain may inhibit
RANKL gene transcription through altering chromatin interactions with
the RANKL promoter. By defining the mechanisms involved in strain
regulation of osteoclast formation we hope to generate new paradigms
for understanding how cells convert mechanical information into
biological effects.

RESEARCH INTERESTS of Janet Rubin: Mechanical and hormonal control of
bone remodeling, gene therapy systems, tumor metastases in bone.


[5] December 7, 2004 Seminar

SPEAKER: Peter Bullough MD, Director of Laboratory Medicine, Hospital
for Special Surgery, New York, NY; Professor of Pathology, Cornell
Medical School, New York, NY

TOPIC: Bone and Subchondral Bone Involvement in the Etiology of Arthritis

PLACE AND TIME: Room 9204, CUNY Graduate Center, 7:00 PM

ABSTRACT: Focal degenerative changes occur in some joints very early
in life. These changes in the articular cartilage appear to occur on
the unloaded, rather than loaded, areas of the joint. Just as unused
bone and unused muscle atrophy, so may unused cartilage. If these
unloaded structures were never subjected to mechanical stress,
degeneration at these sites perhaps would not be important. However,
bones, including their articular ends, are in a constant state of
change through the process of remodeling, which continues throughout
life. Joint surfaces are not, in general, spherical, and therefore
must be incongruent during most of their arc of movement. In the
young person, this incongruity maintains physiologic loading and
joint nutrition. Studies have shown age-related changes in the
remodeling process that lead to increasing joint congruity in old
age. These age-related increases in congruity may result in a
redistribution of load in the joint such that there is an increased
stress on formerly unloaded atrophic cartilage. Arthritis always
results in a change in joint shape. It is suggested that a change in
shape caused by a disturbance in the remodeling process may itself be
an important contributing cause of osteoarthritis.

RESEARCH INTERESTS of Peter Bullough: "I have had a long-time
interest in the question 'Why do people get arthritis?' The study
material has been the joints resected in joint replacement, which
account for around 30% of all orthopaedic procedures where I work."


[6] "Pinch Hitter"

In the Fall 2004 Bone Seminar series we will be experimenting with
the use of a pinch hitter. If, for any reason, the designated speaker
cannot speak on a particular evening, the pinch hitter will
substitute if s/he does not have a previous commitment. The
designated pinch hitter will fulfill that role for only one seminar
series. If the pinch hitter does not speak in the series for which
s/he is designated, s/he will have a regularly scheduled seminar in
the following series. Thus the pinch hitter for the Fall 2004 series,
Luis Cardoso Landa, if he is not called upon to fill in on September
28, October 26, November 16, or December 7, will present a Spring
2005 Seminar.

SPEAKER: Luis Cardoso Landa PhD, Postdoctoral Research Fellow,
Department of Orthopaedics, Mount Sinai School of Medicine, New York,

TOPIC: On the Ultrasonic Characterization of Anisotropic Cancellous
Bone: An In Vitro Experimental and Theoretical Study Based on a
Modified Biot's Theory

ABSTRACT: Currently, the approach most widely used to examine bone
loss is bone densitometry, which measures bone mass density by x-ray
absorptiometry. Recently bone ultrasound attenuation (BUA) has seen
wider clinical use. However, osteoporosis is not only characterized
by a decreased bone mass density, but also by changes in the
microstructure. These mass/density-based approaches cannot show the
microarchitectural aspects of cancellous bone that are key to fully
describing bone's mechanical integrity.

In the material sciences field, ultrasonic wave propagation is a
widely used nondestructive test to estimate the anisotropic
mechanical properties of a media in an accurate manner. An acoustic
wave is a mechanical disturbance reflecting the elasticity of the
material where it is propagated. In a poroelastic media, wave
velocity is affected by the mass quantity and the spatial
distribution of the solid and fluid constituting the composite. If
the porous media exhibit different mechanical properties for
different directions of the space (mechanical anisotropy), it will
accordingly exhibit different ultrasonic velocities (acoustic
anisotropy); see figure at


Nevertheless, a complex relationship exists between acoustic and
mechanical properties in cancellous bone. The intimate processes
determining the ultrasonic wave propagation phenomena in porous media
are not only the consequence of elastic phenomenon, but also reflect
inertial and viscous effects due to the interaction between the solid
and fluid phases, which are frequency-dependent.

Recently, an experimental and theoretical study to understand
ultrasonic wave propagation on anisotropic cancellous bone was
developed. In the experimental studies, human and bovine cancellous
bones from different skeletal sites, exhibiting a large variability
in porosity and microstructure, were evaluated in multiple
directions. The porosity (and correlatively the bone mass density)
was found to be a low predictor of the velocities and the mechanical
properties of cancellous bone. As the variability in measured wave
velocities was hypothesized related to the microstructure of bone, a
novel architectural-density-based model of wave propagation was
developed based on the Biot's theory. This model describes the
velocity of waves as a function of porosity, structural parameters,
tissue properties, and frequency of propagated ultrasonic waves.

The predictability of the measured velocities and mechanical
properties for the different orthogonal directions of the samples
analyzed as a function of density and microstructure was highly
improved, when compared to the density-based approach. Better
estimation of bone mechanical properties is expected to result in
enhanced discrimination of osteoporotic and nonosteoporotic bone.
This approach provides the potential to use ultrasound measurements
in bone to examine tissue architecture in addition to bone mass.

RESEARCH INTERESTS of Luis Cardosa: The bone mechanotransduction
processes regulated by osteocytes and the assessment of bone
mechanical properties through different experimental, mathematical,
and computational approaches.


[7] Questions and Feedback Contact

Stephen C. Cowin PhD
New York Center for Biomedical Engineering
Departments of Biomedical and Mechanical Engineering
School of Engineering
The City College of New York
138th Street and Convent Avenue
New York, NY 10031-9198, USA

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

(212) 799-7970 (Office at Home)



For bone research information, visit .
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 or

Stephen C. Cowin
New York Center for Biomedical Engineering
Departments of Biomedical and Mechanical 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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