Use of a homozygous G608G progeria mouse model for degenerative joint diseases research

May 11, 2020

BOSTON - Hutchinson-Gilford Progeria Syndrome (HGPS) is a fatal condition that is especially prevalent in the skin, cardiovascular and the musculoskeletal systems. There exists a wide gap between existing knowledge of the disease and a potential treatment or cure.

In a study published today in the journal Proceedings of the National Academies of Science, researchers led by Ara Nazarian, PhD, a principal investigator in the Center for Advanced Orthopaedic Studies at BIDMC, investigated the musculoskeletal phenotype of the homozygous G608G BAC-transgenic progeria mouse model, developed at Dr. Collins' lab at the National Institutes of Health, and determined the phenotypic changes of these mice after a five-arm preclinical trial of different treatment combinations with lonafarnib, pravastatin, and zoledronic acid.

"We observed that Lonafarnib did not improve bone or cartilage indices; however, treatment combinations with pravastatin and zoledronic acid significantly improved bone mechanical properties and cartilage structural parameters," said Nazarian.

The changes demonstrated in the cortical bone structure, rigidity and strength of the HGPS G608G mouse model may increase the risk for bending and deformation of bones, which could result in the skeletal dysplasia characteristic of HGPS. Cartilage abnormalities seen in this model resemble the changes observed in age-matched wild type animals, such as decreased cartilage thickness and volume. Such changes might mimic prevalent degenerative joint diseases, including osteoarthritis (OA), in the elderly.

More animal studies will be necessary before investigating the ability of this disease model to help with OA studies. But Nazarian is optimistic about the possibilities offered by this animal model.

"Osteoarthritis is a chronic debilitating disease that degrades articular cartilage and is one of the most common causes of chronic disability and pain in the elderly," said Cubria, previously a postdoctoral fellow at BIDMC and Harvard Medical School. "Accelerated aging animal models, such as this mouse model could offer a meaningful opportunity to study degenerative joint diseases."

In addition to Nazarian, coauthors include co-lead authors M. Belen Cubria and Sebastian Suarez, Aidin Masoudi, Ramin Oftadeh, Pramod Kamalapathy, Lamya Karim, and Brian D. Snyder, all of BIDMC; and Amanda DuBose, Michael R. Erdos, Wayne A. Cabral, and Francis S. Collins, of the National Institutes of Health.
-end-
This work was supported by the National Institutes of Health Loan Repayment Program, and The Progeria Research Foundation.

About Beth Israel Deaconess Medical Center

Beth Israel Deaconess Medical Center is a patient care, teaching and research affiliate of Harvard Medical School and consistently ranks as a national leader among independent hospitals in National Institutes of Health funding.

BIDMC is in the community with Beth Israel Deaconess Hospital-Milton, Beth Israel Deaconess Hospital-Needham, Beth Israel Deaconess Hospital-Plymouth, Anna Jaques Hospital, Cambridge Health Alliance, Lawrence General Hospital, Signature Healthcare, Beth Israel Deaconess HealthCare, Community Care Alliance and Atrius Health. BIDMC is also clinically affiliated with the Joslin Diabetes Center and Hebrew Rehabilitation Center and is a research partner of Dana-Farber/Harvard Cancer Center and the Jackson Laboratory. BIDMC is the official hospital of the Boston Red Sox. For more information, visit http://www.bidmc.org.

BIDMC is part of Beth Israel Lahey Health, a new health care system that brings together academic medical centers and teaching hospitals, community and specialty hospitals, more than 4,000 physicians and 35,000 employees in a shared mission to expand access to great care and advance the science and practice of medicine through groundbreaking research and education.

Beth Israel Deaconess Medical Center

Related Health Articles from Brightsurf:

The mental health impact of pandemics for front line health care staff
New research shows the impact that pandemics have on the mental health of front-line health care staff.

Modifiable health risks linked to more than $730 billion in US health care costs
Modifiable health risks, such as obesity, high blood pressure, and smoking, were linked to over $730 billion in health care spending in the US in 2016, according to a study published in The Lancet Public Health.

New measure of social determinants of health may improve cardiovascular health assessment
The authors of this study developed a single risk score derived from multiple social determinants of health that predicts county-level cardiovascular disease mortality.

BU study: High deductible health plans are widening racial health gaps
The growing Black Lives Matter movement has brought more attention to the myriad structures that reinforce racial inequities, in everything from policing to hiring to maternal mortality.

Electronic health information exchange improves public health disease reporting
Disease tracking is an important area of focus for health departments in the midst of the COVID-19 pandemic.

E-health resource improves men's health behaviours with or without fitness facilities
Men who regularly used a free web resource made significantly more health changes than men who did not, finds a new study from the University of British Columbia and Intensions Consulting.

Mental health outcomes among health care workers during COVID-19 pandemic in Italy
Symptoms of posttraumatic stress disorder, depression, anxiety and insomnia among health care workers in Italy during the COVID-19 pandemic are reported in this observational study.

Mental health of health care workers in china in hospitals with patients with COVID-19
This survey study of almost 1,300 health care workers in China at 34 hospitals equipped with fever clinics or wards for patients with COVID-19 reports on their mental health outcomes, including symptoms of depression, anxiety, insomnia and distress.

Health records pin broad set of health risks on genetic premutation
Researchers from the University of Wisconsin-Madison and Marshfield Clinic have found that there may be a much broader health risk to carriers of the FMR1 premutation, with potentially dozens of clinical conditions that can be ascribed directly to carrying it.

Attitudes about health affect how older adults engage with negative health news
To get older adults to pay attention to important health information, preface it with the good news about their health.

Read More: Health News and Health Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.