A team of researchers from the University of Delaware (UD) and the University of Pennsylvania has clarified details on the structure and function of fibro-cartilaginous tissues. Their work could aid in the development of improved strategies to treat injuries such as meniscus tears…as well as new therapies for osteoarthritis and age-related degeneration. Their findings are reported in Nature Materials.
In the January 4, 2016 news release, Dawn Elliott, Ph.D., professor and chair of UD’s Department of Biomedical Engineering, explained that “fibro-cartilaginous tissues are primarily made up of long, aligned fibers that confer strength and stiffness. It turns out, however, that they also have small non-fibrous regions, known as microdomains, that behave very differently from the fibrous areas.”
“Dr. Elliott turned to Randall Duncan, professor in UD’s Department of Biological Sciences, for help in addressing the issue of cell signaling. With Duncan, the team found that the cells in the microdomains evidenced very high calcium signaling, while calcium signals switched on and off under mechanical loading in the fibrous regions.”
“This told us that cells in these two regions behave very differently when the tissue is stretched, which is critical information in the development of therapies to treat disease, ” said Dr. Elliott.
Then, another researcher was brought in: Robert Mauck, Ph.D., associate professor of orthopedic surgery and bioengineering in the Perelman School of Medicine at the University of Pennsylvania.
As indicated in the news release, “Dr. Mauck and his team created a platform to study microdomain effects under normal and pathological conditions, enabling the researchers to investigate physical structure, mechanical loading and cell signaling under both actual and engineered conditions.”
Drs. Elliott and Mauck told OTW, “We observed in histological sections that the ‘idealized’ aligned fiber structure of many dense connective tissues is not an accurate description of the actual structure. Instead, we found that there are micro domains of non-fibrous proteoglycan rich proteins throughout these tissues. Based on this observation, we asked ourselves what the function of those micro domains might be, and how they impacted the cells embedded in the tissue that are responsible for remodeling and repair during physiological loading activities.”
“We were surprised by how dramatically different the mechanical behavior and cell signaling activities were in these two regions (fibrous and proteoglycan micro domains). We were also surprised to find the pronounced growth of the micro domains with age, disease, and body mass index in humans.”
“This work is important given that the meniscus (and intervertebral disc and other fibrocartilages) are loaded and the cells within these tissues respond to load by remodeling or repairing damage. Our findings suggest that the response of the cells in the two regions may alter how effectively they respond to these mechanical loading cues, and this may promote further degeneration. Our engineered constructs that contain these micro domains and effectively mimic the behavior of native tissue will be an important tool for the development of drug and physical therapies to promote tissue repair.”
