Breaking News
March 24, 2018 - Waning Vaccine Protection May Be Driving Rise in U.S. Mumps Cases
March 24, 2018 - Folic Acid in Utero Tied to Food Allergy Risk
March 24, 2018 - Trial shows safety of drugs for irregular heartbeat patients undergoing treatment
March 24, 2018 - Penn State psychologists shed light on false memories in older adults
March 24, 2018 - Patients who self-discharge should be viewed more positively, say researchers
March 24, 2018 - Wearable brain scanner enables brain imaging whilst moving
March 24, 2018 - Trump Signs $1.3 Trillion Spending Bill, Averts Shutdown
March 24, 2018 - Two drugs prevent heart problems in breast cancer patients
March 24, 2018 - Research provides better understanding of how some cancer cells resist treatment
March 24, 2018 - Certain nutrients found in food may help reduce symptoms of psychotic illness
March 24, 2018 - AbbVie Announces Positive Topline Results from Second Phase 3 Study Evaluating Investigational Elagolix in Women with Uterine Fibroids
March 24, 2018 - AHRQ Is in Trouble | Medpage Today
March 24, 2018 - Could a pap test spot more than just cervical cancer?
March 24, 2018 - Men have greater hospital readmission risk following firearm injury, study shows
March 24, 2018 - Pediatric psychologist shares 11 warning signs of childhood depression
March 24, 2018 - OncoBreak: ‘I Was Normal Once’; Ending Cervical Cancer; Mammo Controversy
March 24, 2018 - Gum Disease by the Numbers
March 24, 2018 - Studies show tool can identify individual needs, supports to help youths with autism, intellectual disabilities
March 24, 2018 - Study reveals cause of extreme nausea in pregnancy
March 24, 2018 - New findings highlight need to reconsider cervical cancer screening guidelines
March 24, 2018 - Smartwatch App Might Help Detect A-Fib
March 24, 2018 - TAVR Reasonable for Low-Flow, Low-Gradient Aortic Stenosis
March 24, 2018 - Kids with severe brain injuries may develop ADHD: study
March 24, 2018 - Researchers explore ways to help older adults taper off and stop using sedatives
March 24, 2018 - Back pain being mismanaged globally
March 24, 2018 - Fingerprint test accurately and noninvasively detects heroin, cocaine users
March 24, 2018 - Leading experts to promote cardiovascular health at EuroPrevent 2018
March 24, 2018 - A Role for Rituximab in Lupus?
March 24, 2018 - New osteoarthritis genes discovered
March 24, 2018 - Maternal intake of DHA supplement linked to higher fat-free body mass in children
March 24, 2018 - Royal College of Pathologists‘ bulletin provides summary of Tissue Handling Workshop
March 24, 2018 - Maternal alcohol use early in pregnancy may be risk factor for infant abdominal malformation
March 24, 2018 - Savara Initiates Phase 2a Clinical Study of Molgradex for the Treatment of NTM Lung Infection
March 24, 2018 - Accelerated WBI Should be the Norm for Most Breast Cancers
March 24, 2018 - Experts seek to standardize treatments for childhood rheumatic diseases
March 24, 2018 - Foil-based measuring chip rapidly detects Legionella
March 24, 2018 - Bariatric surgery linked to positive outcomes in very obese adolescents with type 2 diabetes
March 24, 2018 - Obesity and severe obesity continue to rise among U.S. adults
March 24, 2018 - Missed hospital appointments increase after spring clock change in the UK
March 24, 2018 - Researchers explore ways to manage and prevent falls in older adults with dementia
March 24, 2018 - Are there risks from secondhand marijuana smoke? Early science says yes.
March 24, 2018 - NUST MISIS researchers produce elastic metal rods for scoliosis treatment
March 24, 2018 - New University of Bath project seeks to make injections safer
March 24, 2018 - Higher-dose RT does not improve survival but reduces recurrence risk for prostate cancer patients
March 24, 2018 - Researchers examine link between knee pain and depression in older adults
March 24, 2018 - FDA Alert: BD Vacutainer Blood Collection Tubes by Becton, Dickinson and Company (BD): Class I Recall
March 24, 2018 - Daytime Sleepiness Linked to Amyloid Accumulation Without Dementia
March 24, 2018 - Energy storehouses in the brain may be source of Alzheimer’s, targets of new therapy
March 24, 2018 - Praising people with autism shows promise for producing more exercise
March 24, 2018 - Using harmless red or infrared light to diagnose breast cancer
March 24, 2018 - Clash over abortion hobbles a health bill. Again. Here’s how.
March 23, 2018 - Virtual nature environment could be new way to recover from stress
March 23, 2018 - New study identifies key cellular mechanisms behind vascular aging in mice
March 23, 2018 - Nightmares Common Among U.S. Troops, But Seldom Reported
March 23, 2018 - Another Record Low for Tuberculosis in U.S.
March 23, 2018 - Changes in the eye connected to a decline in memory
March 23, 2018 - Radiologist creates dramatic teaching tool using power of VR
March 23, 2018 - Grilled meat could be raising the risk of hypertension finds study
March 23, 2018 - Mutations found in bassoon gene may help explain cause of rare brain disorder
March 23, 2018 - Childhood Brain Injuries May be Linked to ADHD Years Later
March 23, 2018 - Why treating addiction with medication should be carefully considered
March 23, 2018 - Researchers make key discovery about cellular pathway linked to myriad of diseases
March 23, 2018 - Researchers uncover cause of rare childhood neurodegenerative disease
March 23, 2018 - Measles infection in early childhood could contribute to later COPD
March 23, 2018 - Opioid painkiller is top prescription in 11 states
March 23, 2018 - Sienna Biopharmaceuticals Announces First Patient Dosed In Proof-of-Concept Trial of Topical By Design™ JAK Inhibitor SNA-125 for Atopic Dermatitis
March 23, 2018 - In Teen Girls, Neural Patterns May Drive Emotional Resilience
March 23, 2018 - Gene-based test for urine detects, monitors bladder cancer
March 23, 2018 - BD to introduce new digital solution for IV chemotherapy administration process at EAHP 2018
March 23, 2018 - New computational method helps to identify tumor cell mutations with greater accuracy
March 23, 2018 - Researchers identify potential obesity treatment in freezing hunger-signaling nerve
March 23, 2018 - Wales participates in the 100,000 Genomes Project
March 23, 2018 - 24-Hr Paging Cuts ED Visits for Kids with Endocrine Issues
March 23, 2018 - The brain learns completely differently than we’ve assumed since the 20th century
March 23, 2018 - Less nutritious diet mainly contributes to Type 2 diabetes among U.S.-based South Asians
March 23, 2018 - Stony Brook Medicine expert provides tips for healthy diet to decrease cancer risk
March 23, 2018 - New findings could have revolutionary impact on quality of life of older people
March 23, 2018 - Restoring enzyme may help reverse effects of vascular aging, study shows
March 23, 2018 - Protein profiling reveals new prostate cancer mechanisms
March 23, 2018 - Depression may be linked to increased risk of atrial fibrillation
Acute treatment suppresses posttraumatic arthritis in ankle injury

Acute treatment suppresses posttraumatic arthritis in ankle injury

image_pdfDownload PDFimage_print
Acute treatment suppresses posttraumatic arthritis in ankle injury
Amobarbital treatment (right) could help protect cartilage to prevent arthritis after joint injuries. Credit: M.C. Coleman et al., Science Translational Medicine (2018)

A University of Iowa study has identified a method for inhibiting the occurrence of an aggressive form of arthritis that frequently develops following a severe traumatic injury. The preclinical work demonstrates the potential for preventing posttraumatic osteoarthritis (PTOA) by targeting very early damage after fractures in an animal model of this type of injury. These types of fractures in a load-bearing joint can lead to arthritis as quickly as two years after injury.

PTOA is present in some 5.6 million people in the United States. The disease occurs when cartilage is destroyed in a joint, leading to life-long pain and disability. The young and active patients who are disproportionately likely to experience these injuries are not good candidates for joint replacements, so preventing PTOA in this group is a particularly compelling need.

“The time to complete joint destruction can be as fast as two to four years,” says the study’s corresponding author, Mitchell Coleman, PhD, research assistant professor of orthopedics and rehabilitation in the UI Carver College of Medicine. “That can be devastating for an 18-year-old who injures an ankle falling off a ladder or playing sports.”

Previous work has shown that relatively few chondrocytes—the cells that make up healthy cartilage tissue—are killed at the moment of impact when a joint is fractured. Instead, cell death increases in the 48 hours following the injury, suggesting that biologic activity unleashed by the impact may contribute to early causes of disease.

The University of Iowa study, published Feb. 7 in Science Translational Medicine, focused on reducing oxidative stress in the mitochondria of chondrocytes after injury. Mitochondria are organelles that serve as the powerplant of a cell and are also an important biological source of oxidants. During normal mitochondrial function, only small, relatively innocuous concentrations of oxidants are produced.

The lab of James Martin, PhD—senior author of the study and UI associate professor of orthopedics and rehabilitation and biomedical engineering—has a long-standing research focus on severe mechanical injuries that lead to intense increases in mitochondrial metabolism. These increases result in larger, more damaging concentrations of oxidants and oxidative damage, capable of contributing to rapid PTOA development.

Acute treatment suppresses posttraumatic arthritis in ankle injury
Amobarbital treatment (right) could help protect cartilage to prevent arthritis after joint injuries. Credit: M.C. Coleman et al., Science Translational Medicine (2018)

Using a pig model of ankle fracture, the researchers employed two approaches to limit oxidative damage in the chondrocytes: inhibiting mitochondrial metabolism with amobarbital, and boosting antioxidants in the chondrocytes with N-acetylcysteine (NAC).

“We demonstrated that the posttraumatic osteoarthritis that occurs in an ankle after a severe injury can be significantly blunted by inhibiting mitochondrial metabolism or adding key antioxidants immediately after injury,” Coleman says. “These treatments were only given twice, once right after injury and once a week later. No chronic therapy was used. Our data suggests that there might be a way to treat people acutely after they break their ankle to prevent PTOA.”

By using a pig model instead of the customary mouse model, the researchers were able to closely mimic the treatment a person would receive following a traumatic ankle fracture and test the safety and effectiveness of the treatment in a large animal model. This approach enhances the translational possibilities of the researchers’ work.

The group has applied for grant support to conduct preliminary clinical trials of the approach at multiple institutions.

In addition to Coleman and Martin, the team included UI researchers Jessica Goetz, Marc Brouillette, Dong Rim Seol, Michael Willey, Emily Petersen, Nathan Hendrickson, Jocelyn Compton, Behnoush Khorsand, Angie Morris, Aliasger Salem, and Douglas Fredericks. The team also included Todd McKinley from Indiana University and Hope Anderson from Wellesley College.

The research was supported in part by funding from the U.S. Department of Defense and the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health.

Several of the research team, including Coleman and Martin, are inventors on a patent held by the University of Iowa Research Foundation that covers the use of the reverse thermal hydrogels for prevention of PTOA. Morris serves on the advisory board of Cartilagen LLC, and Martin serves as scientific advisor to Cartilagen LLC, which licenses the patent.

Explore further:
New research could personalize medicine for arthritis patients

More information:
M.C. Coleman el al., “Targeting mitochondrial responses to intra-articular fracture to prevent posttraumatic osteoarthritis,” Science Translational Medicine (2018). … scitranslmed.aan5372

Journal reference:
Science Translational Medicine

Provided by:
University of Iowa

Tagged with:

About author

Related Articles