Adenosine Helps Regrow Cartilage in Osteoarthritis

Injections of a natural ‘energy’ molecule prompted regrowth of almost half of the cartilage lost with aging in knees, a new study in rodents shows.

#arthritis #osteoarthritis #adenosine

Carmen Corciulo, Cristina M. Castro, Thomas Coughlin, Samson Jacob, Zhu Li, David Fenyö, Daniel B. Rifkin, Oran D. Kennedy, Bruce Neil Cronstein. Intraarticular injection of liposomal adenosine reduces cartilage damage in established murine and rat models of osteoarthritis. Scientific Reports, 2020; 10 (1) DOI: 10.1038/s41598-020-68302-w

https://www.nature.com/articles/s41598-020-68302-w

Scientists build ‘mechanically active’ DNA material

Contact: Melissa Van De Werfhorst

melissa@engineering.ucsb.edu

805-893-4301

University of California – Santa Barbara

 

 

 

Researchers at UC Santa Barbara designed a ‘smart’ material made of DNA that responds with movement when stimulated

 

Artificial muscles and self-propelled goo may be the stuff of Hollywood fiction, but for UC Santa Barbara scientists Omar Saleh and Deborah Fygenson, the reality of it is not that far away. By blending their areas of expertise, the pair have created a dynamic gel made of DNA that mechanically responds to stimuli in much the same way that cells do. The results of their research were published online in the Proceedings of the National Academy of Sciences.

 

“This is a whole new kind of responsive gel, or what some might call a ‘smart’ material,” said Saleh, associate professor of materials, affiliated with UCSB’s Biomolecular Science and Engineering program. “The gel has active mechanical capabilities in that it generates forces independently, leading to changes in elasticity or shape, when fed ATP molecules for energy—much like a living cell.”

 

Their DNA gel, at only 10 microns in width, is roughly the size of a eukaryotic cell, the type of cell of which humans are made. The miniscule gel contains within it stiff DNA nanotubes linked together by longer, flexible DNA strands that serve as the substrate for molecular motors.

 

“DNA gives you a lot more design control,” said Fygenson, associate professor of physics and also affiliated with UCSB’s BMSE program. “This system is exciting because we can build nano-scale filaments to specifications.” Using DNA design, she said, they can control the stiffness of the nanotubes and the manner and extent of their cross-linking, which will determine how the gel responds to stimuli.

 

Using a bacterial motor protein called FtsK50C, the scientists can cause the gel to react in the same way cytoskeletons react to the motor protein myosin—by contracting and stiffening. The protein binds to predetermined surfaces on the long linking filaments, and reels them in, shortening them and bringing the stiffer nanotubes closer together. To determine the gel’s movement the scientists attached a tiny bead to its surface and measured its position before and after activation with the motor protein.

 

The breakthrough, said Saleh, is that this gel “quantitatively shows similar active fluctuations and mechanics to cells.”

 

“This new material could provide a means for controllably testing active gel mechanics in a way that will tell us more about how the cytoskeleton works,” Saleh said. Like a cell, which consumes adenosine triphosphate (ATP) for energy, the DNA gel’s movement runs on ATP, allowing for faster, stronger mechanics than other smart gels based on synthetic polymers.

 

“The development of active gels represents a water-shed event for the broader materials community,” commented Craig Hawker, director of the Materials Research Laboratory at UCSB: an NSF MRSEC, which provided seed money for their research. “By exploiting cellular building blocks, it offers unique design parameters when compared to existing gel systems that can be used in a wide range of both established biomedical applications as well as totally new applications.”

 

The project has potential applications for a variety of fields, including smart materials, artificial muscle, understanding cytoskeletal mechanics and research into nonequilibrium physics, as well as DNA nanotechnology. Long-term implications of this research are significant, Hawker added, with the final result being “a fundamental breakthrough in soft-materials science and engineering.”

 

Having created a gel that can replicate contractions, Saleh and Fygenson are now looking to refine their technique and enable distinct movements, such as twisting and crawling, or using other motor proteins that would allow the gel to mimic other cell behaviors, such as shape-shifting and dividing.

 

“Biology provides a wide range of motors that we have only begun to explore,” Saleh said.

 

“And the suite of nanostructure designs and geometries at our disposal is nearly limitless,” echoed Fygenson.

 

 

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Increased dietary fructose (high fructose corn syrup) linked to elevated uric acid levels and lower liver energy stores

Contact: Dawn Peters sciencenewsroom@wiley.com 781-388-8408 Wiley

Obese patients with type 2 diabetes who consume higher amounts of fructose display reduced levels of liver adenosine triphosphate (ATP)—a compound involved in the energy transfer between cells. The findings, published in the September issue of Hepatology, a journal of the American Association for the Study of Liver Diseases, indicate that elevated uric acid levels (hyperuricemia) are associated with more severe hepatic ATP depletion in response to fructose intake.

This exploratory study, funded in part by grants from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), also suggests that uric acid levels may serve as a marker for increased fructose consumption and hepatic ATP depletion. Uric acid is produced by the breakdown of purines, natural substances commonly found in foods. According to the authors, increased dietary fructose can alter the body’s metabolism and energy balance. Energy depletion in the liver may be associated with liver injury in patients with non-alcoholic fatty liver disease (NAFLD) and in those at risk for developing this metabolic condition.

Fructose is a simple sugar that fuels the body, and is found in fruits and vegetables. High fructose corn syrup—a mixture of glucose and fructose—is used as a sweetener in consumer food products such as bread, cereal, and soda. Prior research reports that fructose consumption in the U.S. has more than doubled in the past 30 years. In fact, studies have shown that Americans’ fructose intake climbed from 15 grams per day in the early 1900s to 55 grams per day in 1994, which experts believe stems from an increase in soft drink consumption.

“There is an alarming trend of increased rates of obesity, type 2 diabetes and NAFLD in the U.S.,” said lead author Dr. Manal Abdelmalek from Duke University Medical Center. “Given the concurrent rise in fructose consumption and metabolic diseases, we need to fully understand the impact of a high-fructose diet on liver function and liver disease.”

For the present study, 244 obese and diabetic adults from the Look AHEAD Study were evaluated, with dietary fructose consumption estimated by the food frequency questionnaire. Liver ATP and uric acid levels were measured in 105 patients who participated in the Look AHEAD Fatty Liver Ancillary Study. Researchers assessed the change in liver ATP content using an IV fructose challenge in 25 subjects, comparing patients with low fructose consumption (less than 15 grams per day) to those with high fructose consumption (greater than 15 grams per day).

The team found that participants with a high intake of dietary fructose had lower liver ATP levels at baseline and a greater change in ATP content following the fructose challenge than those who consumed a lower amount of fructose. Patients with high uric acid levels (5.5 mg/dL or more) displayed lower ATP stores in response to fructose.

Dr. Abdelmalek concludes, “High fructose consumption and elevated levels of uric acid are associated with more severe depletion of liver ATP. Our findings suggest that increased dietary fructose intake may impair liver “energy balance.” Further research to define the clinical implications of these findings on metabolism and NAFLD is necessary.” The authors highlight the importance of public awareness of the risks associated with a diet high in fructose.

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This study is published in Hepatology. Media wishing to receive a PDF of this articles may contact sciencenewsroom@wiley.com.

Full Citation: “Higher Dietary Fructose Is Associated with Impaired Hepatic ATP Homeostasis in Obese Individuals with Type 2 Diabetes.” Manal F. Abdelmalek, Mariana Lazo, Alena Horska, Susanne Bonekamp, Edward W. Lipkin, Ashok Balasubramanyam, John P. Bantle, Richard J. Johnson, Anna Mae Diehl, Jeanne M. Clark, and the Fatty Liver Subgroup of the Look AHEAD Research Group. Hepatology; (DOI: 10.1002/hep.25741); Print Issue Date: September, 2012. URL: http://onlinelibrary.wiley.com/doi/10.1002/hep.25741/abstract

Author Contact:

To arrange an interview with Dr. Abdelmalek, please contact Rachel Bloch with Duke University at rachel.bloch@duke.edu or at +1 919-419-5069.

About the Journal:

Hepatology is the premier publication in the field of liver disease, publishing original, peer-reviewed articles concerning all aspects of liver structure, function and disease. Each month, the distinguished Editorial Board monitors and selects only the best articles on subjects such as immunology, chronic hepatitis, viral hepatitis, cirrhosis, genetic and metabolic liver diseases and their complications, liver cancer, and drug metabolism. Hepatology is published on is published by Wiley on behalf of the American Association for the Study of Liver Diseases (AASLD). For more information, please visit http://wileyonlinelibrary.com/journal/hep.

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