Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Seeing the Knee in a New Light: Fluorescent Probe Tracks Osteoarthritis Development

05.02.2015

Study findings may lead to improved method to detect early to moderate osteoarthritis

A fluorescent probe may make it easier to diagnose and monitor osteoarthritis, a painful joint disease affecting nearly 27 million Americans. The disease is often detected late in development after painful symptoms occur. Earlier diagnosis might lead to better management and patient outcomes. A new study reports that a fluorescent probe tracked the development of osteoarthritis in male mice, brightening as the disease progressed. The findings are published in the February issue of Arthritis & Rheumatology.


National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

X-ray image of osteoarthritic knees.

In this case, the “probe” was a harmless fluorescent molecule that detected the activity leading to cartilage loss in the joint, the key characteristic of osteoarthritis. This lab and mouse study, led by researchers from Tufts University School of Medicine (TUSM) and the Sackler School of Graduate Biomedical Sciences at Tufts, is the first to demonstrate that near-infrared fluorescence – a specific type of light invisible to the human eye but possible to see with optical imaging – can be used to detect osteoarthritis changes over time. The new approach might also help analyze the effectiveness of osteoarthritis drugs, leading to improved treatments.

“Patients are frequently in pain by the time osteoarthritis is diagnosed. The imaging tests most frequently used, X-rays, don’t indicate the level of pain or allow us to directly see the amount of cartilage loss, which is a challenge for physicians and patients,” said co-first author Averi A. Leahy, B.A., an M.D./Ph.D. student in the medical scientist training program at TUSM and the Sackler School.

“The fluorescent probe made it easy to see the activities that lead to cartilage breakdown in the initial and moderate stages of osteoarthritis, which is needed for early detection and adequate monitoring of the disease. To measure the probe’s signal, we used an optical imaging system, to non-invasively look inside the knee,” said co-first author Shadi A. Esfahani, M.D., M.P.H., post-doctoral fellow in the division of nuclear medicine and molecular imaging at Massachusetts General Hospital, and in the department of radiology at Harvard Medical School.

The right knees of 54 mice were affected by injury-induced osteoarthritis and served as the experimental group (the mice received pain medication). The healthy, left knees of the mice served as the control group.

Over a two-month period, the researchers took images of each knee every two weeks to determine if the fluorescent probe emitted a signal. Strikingly, the signal became brighter in the injured right knee, at every examined time point, through the early to moderate stages of osteoarthritis. The probe emitted a lower signal in the healthy left knee, and did not increase significantly over time.

The corresponding and senior author is Li Zeng, Ph.D., associate professor in the department of integrative physiology and pathobiology at TUSM, and member of the cellular, molecular and developmental biology program faculty at the Sackler School. Averi Leahy is one of her students. The work was done in collaboration with Umar Mahmood, M.D., Ph.D., director of the Center for Translational Nuclear Medicine and Molecular Imaging, co-director of Nuclear Medicine and Molecular Imaging, both at Massachusetts General Hospital; and associate professor in the department of radiology at Harvard Medical School.

Zeng reports that the next step is to monitor the fluorescent probe over a longer period of time to determine whether the same results are produced during the late stages of osteoarthritis. She also hopes to use the probe to help develop treatments for animals, as some dogs are prone to osteoarthritis.

Osteoarthritis, the most common type of arthritis, causes pain, swelling, and reduced motion by breaking down cartilage that covers the ends of bones. The disease often results from an injury or long term wear and tear to the hip, hands, or knees. Reducing the burden of osteoarthritis has been a top priority for US public health officials. The National Public Health Agenda for Osteoarthritis, created by the Arthritis Foundation and the Centers for Disease Control and Prevention, calls for more research into osteoarthritis to better understand effective strategies for intervention.

The Zeng laboratory at Tufts studies the mechanisms of tissue formation and degradation to develop effective strategies to treat arthritis. Her team uses tissue engineering techniques to examine approaches that can be used to generate stronger, more stable cartilage tissue that is resistant to inflammation commonly caused by osteoarthritis.

Previous research had identified that an increase in enzymes called matrix metalloproteinases (MMP) contributes to the cartilage degradation that occurs with osteoarthritis. The fluorescent probe was introduced into the knee joint and measured MMP activity.

Additional authors of this study are Carrie K. Hui, B.S., a doctoral student in the cellular, molecular and developmental biology program at the Sackler School; Roshni S. Rainbow, Ph.D., an affiliate in the department of anatomy and basic sciences at Tufts University School of Medicine and former Institutional Research and Academic Career Development (IRACDA) postdoctoral fellow at the Sackler School; Daisy S. Nakamura, B.S., a doctoral student in the cellular, molecular and developmental biology program at the Sackler School; and Brian H. Tracey, Ph.D., professor in the department of electrical and computer engineering at Tufts University School of Engineering. Research reported in this publication was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health (NIH) under award numbers F30AR065866 and R01AR059106, by a research training grant from the National Institute of General Medical Sciences (NIGMS) of the NIH under award number K12GM074869 (IRACDA), and by the National Center for Advancing Translational Sciences of the NIH under award number UL1TR001064. Additional funding was provided by a Tufts Collaborates seed grant, and the National Science Foundation under award number CBET-0966920.

The Institutional Research Career and Academic Development Awards from the NIGMS combine traditional post-doctoral research work with mentored teaching experience at institutions that serve under-represented minorities. The Sackler School’s IRACDA Training in Education and Critical Research Skills (TEACRS) program is a partnership with the University of Massachusetts, Boston; Pine Manor College, and Bunker Hill Community College. It is the only IRACDA-funded program in New England.

Leahy, A. A., Esfahani, S. A., Foote, A. T., Hui, C. K., Rainbow, R. S., Nakamura, D. S., Tracey, B. H., Mahmood, U., & Zeng, L. (February 2015). “Analysis of the Trajectory of Osteoarthritis Development in a Mouse Model by Serial Near-Infrared Fluorescence Imaging of Matrix Metalloproteinase Activities.” Arthritis & Rheumatology, 67(2). DOI: 10.1002/art.38957

About Tufts University School of Medicine and the Sackler School of Graduate Biomedical Sciences
Tufts University School of Medicine and the Sackler School of Graduate Biomedical Sciences at Tufts University are international leaders in innovative medical and population health education and advanced research. Tufts University School of Medicine emphasizes rigorous fundamentals in a dynamic learning environment to educate physicians, scientists, and public health professionals to become leaders in their fields. The School of Medicine and the Sackler School are renowned for excellence in education in general medicine, the biomedical sciences, and public health, as well as for innovative research at the cellular, molecular, and population health level. Ranked among the top in the nation, the School of Medicine is affiliated with six major teaching hospitals and more than 30 health care facilities. Tufts University School of Medicine and the Sackler School undertake research that is consistently rated among the highest in the nation for its effect on the advancement of medical and prevention science.

Contact Information
Siobhan Gallagher
Associate Director, Public Relations
siobhan.gallagher@tufts.edu
Phone: 617-636-6586

Siobhan Gallagher | newswise
Further information:
http://www.tufts.edu/

More articles from Health and Medicine:

nachricht New malaria analysis method reveals disease severity in minutes
14.08.2017 | University of British Columbia

nachricht New type of blood cells work as indicators of autoimmunity
14.08.2017 | Instituto de Medicina Molecular

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Fizzy soda water could be key to clean manufacture of flat wonder material: Graphene

Whether you call it effervescent, fizzy, or sparkling, carbonated water is making a comeback as a beverage. Aside from quenching thirst, researchers at the University of Illinois at Urbana-Champaign have discovered a new use for these "bubbly" concoctions that will have major impact on the manufacturer of the world's thinnest, flattest, and one most useful materials -- graphene.

As graphene's popularity grows as an advanced "wonder" material, the speed and quality at which it can be manufactured will be paramount. With that in mind,...

Im Focus: Exotic quantum states made from light: Physicists create optical “wells” for a super-photon

Physicists at the University of Bonn have managed to create optical hollows and more complex patterns into which the light of a Bose-Einstein condensate flows. The creation of such highly low-loss structures for light is a prerequisite for complex light circuits, such as for quantum information processing for a new generation of computers. The researchers are now presenting their results in the journal Nature Photonics.

Light particles (photons) occur as tiny, indivisible portions. Many thousands of these light portions can be merged to form a single super-photon if they are...

Im Focus: Circular RNA linked to brain function

For the first time, scientists have shown that circular RNA is linked to brain function. When a RNA molecule called Cdr1as was deleted from the genome of mice, the animals had problems filtering out unnecessary information – like patients suffering from neuropsychiatric disorders.

While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the...

Im Focus: RAVAN CubeSat measures Earth's outgoing energy

An experimental small satellite has successfully collected and delivered data on a key measurement for predicting changes in Earth's climate.

The Radiometer Assessment using Vertically Aligned Nanotubes (RAVAN) CubeSat was launched into low-Earth orbit on Nov. 11, 2016, in order to test new...

Im Focus: Scientists shine new light on the “other high temperature superconductor”

A study led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg presents evidence of the coexistence of superconductivity and “charge-density-waves” in compounds of the poorly-studied family of bismuthates. This observation opens up new perspectives for a deeper understanding of the phenomenon of high-temperature superconductivity, a topic which is at the core of condensed matter research since more than 30 years. The paper by Nicoletti et al has been published in the PNAS.

Since the beginning of the 20th century, superconductivity had been observed in some metals at temperatures only a few degrees above the absolute zero (minus...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Call for Papers – ICNFT 2018, 5th International Conference on New Forming Technology

16.08.2017 | Event News

Sustainability is the business model of tomorrow

04.08.2017 | Event News

Clash of Realities 2017: Registration now open. International Conference at TH Köln

26.07.2017 | Event News

 
Latest News

On the way to developing a new active ingredient against chronic infections

21.08.2017 | Life Sciences

Smart Computers

21.08.2017 | Information Technology

A Map of the Cell’s Power Station

18.08.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>