Inside this issue: University of Pennsylvania Penn Center for Musculoskeletal Disorders
PCMD Annual Scientific Sympo- 2
sium, P30 Renewal grant, Spot-
light on PCMD Member research Institute on Aging Annual Retreat –April 28, 2010
Spotlight on PCMD Member 3
research The Penn Center for Muscu- Director of the Maine Center for Function and Vitamin D in
loskeletal Disorders will co- Osteoporosis Research and Adults with Chronic Kidney Dis-
Upcoming Events 4
Education. Dr. Rosen will pre-
sponsor the Institute on Aging ease."
(IOA) 2010 Sylvan M. Cohen sent "Who is Keeping Time? The The annual Poster Session on
Annual Retreat with Poster Ses- Role of Clock Genes in Regulat- Aging will follow the lectures
Penn Center for Musculoskeletal ing Body Composition."
sion on Aging which will take and is open to all who wish to
University of Pennsylvania School of
place April 28, 2010, in Hous- Featured PENN presenters are participate. Prizes will be
Medicine ton Hall here on Penn's cam- Robert J. Pignolo, MD, PhD, awarded to the top posters in
424 Stemmler Hall, 3450 Hamilton pus. Assistant Professor of Medicine, each category.
Walk The title of the retreat will be and Director, Ralston-Penn Registration is required to at-
Philadelphia, PA 19104-6081 "Structurally Sound: Bone Clinic for Osteoporosis & Re- tend and/or present a poster.
Health and Aging" and there will lated Bone Disorders, and Mary Lunch will be provided to those
be a poster session. The retreat Leonard, MD, MSCE, Professor who register.
will take place from 11:30 am— of Pediatrics and Epidemiology. There is no charge to attend
5:30 pm. Dr. Pignolo's presentation will and the public is welcome. For
If you have any news or information Serving as the Sylvan M. Cohen discuss "The Biological Basis for more information about this
that you would like included in the Visiting Scholar is Clifford J. Alternative Approaches to Os- event, please visit:
Rosen, MD, Senior Scientist at teoporosis Treatment" while Dr. http://www.med.upenn.edu/
next issue of this newsletter, please
the Maine Medical Center Re- Leonard will speak about her
email us at:
search Institute and Former work in "Bone Structure, Muscle
Institute on Aging/PCMD Co-Sponsored Pilot Grant Recipients
The University of Pennsylvania Kurt D. Hankenson, D.V.M., M.S., with aging. By extension, he also
Institute on Aging (IOA) has Ph.D., will receive funding for his hypothesizes that activating
awarded ten investigators with pilot grant titled “Notch Signaling Notch signaling will promote bone
one year of funding each for their in Bone Regeneration.” regeneration.
Did you know that funds are avail- pilot grant projects with a start
able to support projects within Hankenson’s grant focuses on The third recipient is Eileen
date of July 1, 2010. Our PCMD Notch signaling, one possible
each Research Core (in addition to has co-sponsored this competi- Shore, Ph.D., whose pilot grant is
explanation for the healing deficit titled “Modulation of Progenitor
the Pilot Grant Program)? For tion along with The Bingham Trust that is observed in muscle, with Cell Differentiation through BMP
more information, please contact and 3 musculoskeletal grants age. Notch signaling is also active Signaling.” Dr. Shore’s pilot grant
the Core Directors- were awarded. during bone regeneration; how- focuses on understanding key
Donald Baldwin, Ph.D.- Olena Jacenko, Ph.D., will receive ever, there has not been a report molecular factors that control
firstname.lastname@example.org,upenn.edu funding to support her project of decreased Notch signaling in differentiation of stem cells and
(microarray) titled “Aging of the Hematopoietic bone associated with age nor the cellular mechanisms that
Niche.” Dr. Jacenko will seek to associating defects in healing regulate specific cell fate deci-
Dawn Elliott, Ph.D.- understand the cause of underly- with alterations in Notch. Hanken- sions and narrow the gap in our
email@example.com ing age-related changes including son hypothesizes that Notch sig- knowledge of these processes
(structure-function biomechanics) reduced bone mass, diminished naling is reduced in aged mesen- that are relevant to aging-related
blood formation, and deficient chymal stem cells (MSC). This bone loss.
Felix Wehrli, Ph.D.-
immune function leading to bone contributes to a decrease in MSC
firstname.lastname@example.org number and function and defec-
(imaging). tive bone regeneration observed
Page 2 The Musculoskeletal Messenger
PCMD Annual Scientific Symposium Scheduled for Nov. 17, 2010
The PCMD is looking forward to speak on Musculoskeletal Re- Last year’s event featured 47
the 7th Annual Scientific Sym- generative Medicine. posters and boasted over 180
posium which will take place on The symposium will include a registrants. We are expecting
November 17, 2010. The key- continental breakfast, moder- another successful event this
note speaker will be Michael J. ated scientific sessions, lunch coming November. Please mark
Yaszemski, M.D., Ph.D., Profes- and poster sessions. your calendar and be sure to
sor of Orthopaedics and Bioen- check the PCMD website in the
The day will conclude with Dr.
gineering at the Mayo Clinic, coming months for updated
Yaszemski’s lecture and the
and the Director of the Tissue information about the sympo-
presentation of poster awards.
Engineering and Biomaterials sium.
Laboratory. Dr. Yaszemski will
PCMD Center Grant Up for Renewal by NIH
The NIH P30 Grant which funds facing with other P30 centers membership category might in- We always welcome your sugges-
our PCMD center is up for re- locally and nationally, improving clude grant writing assistance tions and comments for ways to
newal this summer. Our center is the PCMD website to include and travel grants so that the As- improve the Center so that it may
among the country’s five P30 more information about research sociate Members would be aided better serve you, the muscu-
centers, three of which will be core opportunities and pricing for in attending musculoskeletal loskeletal community here at
competing for renewal this round. members, and questions related research conferences where re- Penn. Therefore, if there are
Recently, PCMD Director Lou to foci for future research. search was being presented. other ideas or initiatives that you
Soslowsky met with Center core Another exciting idea that the Thanks to all PCMD members would like the PCMD to under-
directors and associate directors PCMD leadership is considering who responded to our email re- take, please e-mail us at:
to discuss what goals and objec- is the creation of a PCMD Associ- quests for paper and grant cita- email@example.com.
tives they would like to accom- ate Membership category which tions—these will be incorporated
plish within the next few years. would be open to Penn grad stu- in our progress report to the NIH
These goals include: partnering dents, post-docs and research and serve as important metrics of
with other centers and institutes staff. The benefits of this new our activities and successes.
within the Penn community, inter-
Research Updates from PCMD Members
T1r MRI Studies on Articular Cartilage of Human Knee—Ravinder Reddy, Ph.D.
Osteoarthritis (OA) affects more pain. Because of the long natural MRI, a novel imaging method that Initial data shows a significant
than half of the population above history of OA (10-20 years), vali- has the ability to generate en- (p<0.001) mean T1ρ value in-
the age of 65 and the economic dating the efficacy of potential dogenous contrast that is sensi- crease between the 3 and 9-
costs in the US from OA have disease modifying drugs in hu- tive to in vivo proteoglycan con- month time points for all individu-
been estimated to be more than mans will require a technique tent. To determine the efficacy of als recruited. These preliminary
1% of the gross domestic product. that can directly assess their this method in tracking molecular results show the potential of T1r
A feature of idiopathic OA is the effect on the macromolecular changes in early OA, we are study- MRI in tracking the disease pro-
degradation of proteoglycan mac- matrix. ing correlation between arthro- gression in morphologically intact
romolecules within hyaline articu- Arthroscopy, an invasive proce- scopically confirmed chondro- human cartilage in vivo.
lar cartilage. There is no cure for dure, is currently the gold stan- malacia and proteoglycan-
the disease and treatments pri- dard to diagnose this pathology. induced changes in T1rMRI.
marily focused on alleviating the Our group has developed, T1ρ
Figure 1: Representative
axial patella view of T1r map
overlay. A - Age Matched
control,B - 3 months post
arthroscopy, C- 9 months
post arthroscopy. Color bar
of T1r values in millisec-
A B C
Spring 2010 Page 3
Research Updates from PCMD Members
Identifying mechanical signals for muscle growth-Elisabeth R. Barton, Ph.D.
Hard and soft tissues share important physio- conversion of muscle stretch to an appro-
logical properties. For example, the ability to priate signal for maintaining muscle integ-
convert mechanical load to signals for tissue rity. We utilize both isolated murine skeletal
growth not only makes bones stronger, but muscle and cell culture systems to probe
also helps to maintain skeletal muscle mass. into how the sarcoglycans fit into the load-
For the last few years, my lab has been exam- sensor picture (See figure right). These
ining the membrane complexes that sense studies contribute to understanding the
muscle load. Like most other cell types, the pathogenesis of the muscular dystrophies,
integrin complex, which spans the muscle where mutations in the DGC cause muscle
plasma membrane, senses mechanical fragility and degeneration, and also to find-
forces, and through its links to signal trans- ing ways to maintain muscle mass when
duction cascades, drives muscle growth. How- the tissue lacks load signals, as in bed rest
ever, an additional membrane complex, the or space travel. Support for this research
dystrophin glycoprotein complex (DGC), has includes grants from NIH, NASA, and the
emerged as a complementary mechanical American Heart Association.
signal transduction system for skeletal mus-
cle. The sarcoglycans, which are part of the
DGC appear to be important for regulating the
Above: Model for mechanical sensors in skeletal muscle. The dystrophin
glycoprotein complex is poised to detect mechanical changes. Mechanical
perturbation, induced by stretch or contraction or both (shown in large red
arrows), can cause membrane distortions that are sensed by proteins span-
ning the sarcolemma, including the integrins and sarcoglycans (SG). This
leads to activation of the MAPK pathways (represented by ERK) and also
phosphorylation of SG complex members. FAK is kinase which is likely to
mediate these changes.
Quantification of Age Dependent Molecular Changes in Guinea Pig OA Model using T1ρ MRI-Ravinder Reddy, Ph.D.
Osteoarthritis (OA) is a degenerative and genetic factors. T1ρ MRI is a month old cohort and 5, 7, and 9
joint disease, which causes severe novel imaging method that has the month old cohorts. A non-significant
pain and is associated with compro- ability to generate endogenous con- increase of mean T1ρ (mean p<0.11)
mised quality of life and imparts heavy trast that is sensitive to in vivo pro- was found between the three older
toll on the health care system. Knee teoglycan content which is a key factor cohorts. Analysis of the skewness of
and hip OA cases are primarily contrib- in early stage OA development. the data shows significant differences
uting to chronic disability amongst the (p<0.001) between the 3 month old
elderly population. Currently there is The purpose of this study was to dem- cohort and the three older cohorts.
no cure for the disease and therapeu- onstrate the efficacy of T1ρ MRI in Data demonstrates that proteoglycan
tic interventions are primarily targeted quantifying age-dependent, spontane- loss has already occurred by 5 months
to symptomatic relief. Various animal ous osteoarthritic changes in the of age with late stage morphological
models have been developed to study Dunkin-Hartley guinea pig model over changes (cartilage thinning and loss)
the progression of OA. Guinea pigs are a period of 10 months. Four age occurring by 9 months.
unique in that OA progression occurs cohorts (3, 5, 7, and 9 month old)
spontaneously and develops much were scanned with the T1ρ MRI proto- These studies demonstrate the poten-
quicker than in other models. Age col. Immediately following imaging, tial of T1ρ mapping in quantifying
dependent biochemical analysis of the animals were sacrificed and tissue early molecular changes associated
Dunkin-Hartley guinea pig stifle has was harvested for histological analysis with spontaneous cartilage degenera-
been studied extensively demonstrat- for confirmation of OA. For age- tion by 5 months of age.
ing spontaneous OA progression. dependent T1ρ analysis, a one-tailed
Evidence suggests a multi-factorial unpaired t-test with unequal variance T1ρ MRI coupled with the spontane-
etiology of OA by combinations of was performed to determine signifi- ous OA model potentially enable test-
biomechanical (non-optimal loading cant changes between cohorts. There ing of disease modifying osteoarthritis Please turn to page 4 for image
stresses/trauma), biochemical was a significant (p<0.001) increase drugs in vivo in a time efficient and corresponding to this research
(breakdown of proteoglycan matrix), of mean T1ρ value between the 3 cost effective manner.
Below-Image from Dr. Reddy’s research (story, page 3)
3 month 5 month 7 month 9 month
0 40 140 0 40 140 0 40 120 0 40 180
Figure 1 - Representative T1ρ map overlays of four age cohorts with T1ρ histogram distributions. Color-bar values are in
PCMD Visiting Professorship Sylvan M. Cohen Annual Retreat with Center for Bone Health
Poster Session on Aging 2010
Structurally Sound: Bone Health and Aging
Tuesday, May 18, 2010, 1:00- Friday, May 14, 2010, 12:00-1:00
2:00pm/BRB 251 The 2010 Sylvan M. Cohen Annual Retreat with pm/Room TBA
Scott A. Rodeo, MD Poster Session on Aging will take place April
Optimizing Bone Health in Children
28, 2010, in Houston Hall here on Penn's cam-
“The Role of Mechanical Loading in and Adolescents
Tendon-to-Bone Healing: Our Experi- Catherine Gordon, M.D., MSc, Direc-
The Institute on Aging will be partnering with
ence with Small Animal Models” tor Bone Health Program, Children’s
the Penn Center for Musculoskeletal Disorders
to present the 2010 retreat, with its focus on Hospital Boston
Professor of Orthopaedic Surgery,
Weill Cornell Medical College, New "Structurally Sound: Bone Health and Aging"
York, NY and annual poster session. For more information, contact:
There is no charge to attend and the public is Michael A. Levine, M.D., FAAP, FACP
Attending Orthopaedic Surgeon, New welcome. For more information about this Chief, Division of Endocrinology and
York-Presbyterian Hospital event, please visit: Diabetes
Attending Orthopaedic Surgeon, Hospi- http://www.med.upenn.edu/aging/index.shtml The Children's Hospital of Philadel-
tal for Special Surgery, New York, NY phia
215-590-3618 - phone
215-590-3053 - fax