Tag: cartilage

Categories : Skeletal SystemTags :

Discovery of New Skeletal Tissue Holds Promise for Regenerative Medicine

On By ModernMedia
“Lipocartilage” is a type of supportive skeletal tissue, that consists of densely packed, bubble-like cells containing fat. This image shows a scan of mouse ear lipocartilage stained with a green fluorescent dye. Charlie Dunlop School of Biological Sciences

An international research team led by the University of California, Irvine has discovered a new type of skeletal tissue that offers great potential for advancing regenerative medicine and tissue engineering.

Most cartilage relies on an external extracellular matrix for strength, but “lipocartilage,” which is found in the ears, nose and throat of mammals, is uniquely packed with fat-filled cells called “lipochondrocytes” that provide super-stable internal support, enabling the tissue to remain soft and springy – similar to bubbled packaging material.

The study, published in the journal Science, describes how lipocartilage cells create and maintain their own lipid reservoirs, remaining constant in size. Unlike ordinary adipocyte fat cells, lipochondrocytes never shrink or expand in response to food availability.

“Lipocartilage’s resilience and stability provide a compliant, elastic quality that’s perfect for flexible body parts such as earlobes or the tip of the nose, opening exciting possibilities in regenerative medicine and tissue engineering, particularly for facial defects or injuries,” said corresponding author Maksim Plikus, UC Irvine professor of developmental and cell biology. “Currently, cartilage reconstruction often requires harvesting tissue from the patient’s rib – a painful and invasive procedure. In the future, patient-specific lipochondrocytes could be derived from stem cells, purified and used to manufacture living cartilage tailored to individual needs. With the help of 3D printing, these engineered tissues could be shaped to fit precisely, offering new solutions for treating birth defects, trauma and various cartilage diseases.”

Dr Franz Leydig first recognised lipochondrocytes in 1854, when he noted the presence of fat droplets in the cartilage of rat ears, a finding that was largely forgotten until now. With modern biochemical tools and advanced imaging methods, UC Irvine researchers comprehensively characterised lipocartilage’s molecular biology, metabolism and structural role in skeletal tissues.

They also uncovered the genetic process that suppresses the activity of enzymes that break down fats and reduce the absorption of new fat molecules, effectively locking lipochondrocytes’s lipid reserves in place. When stripped of its lipids, the lipocartilage becomes stiff and brittle, highlighting the importance of its fat-filled cells in maintaining the tissue’s combination of durability and flexibility. In addition, the team noted that in some mammals, such as bats, lipochondrocytes assemble into intricate shapes, like parallel ridges in their oversized ears, which may enhance hearing acuity by modulating sound waves.

“The discovery of the unique lipid biology of lipocartilage challenges long-standing assumptions in biomechanics and opens doors to countless research opportunities,” said the study’s lead author, Raul Ramos, a postdoctoral researcher in the Plikus laboratory for developmental and regenerative biology. “Future directions include gaining an understanding of how lipochondrocytes maintain their stability over time and the molecular programs that govern their form and function, as well as insights into the mechanisms of cellular aging. Our findings underscore the versatility of lipids beyond metabolism and suggest new ways to harness their properties in tissue engineering and medicine.”

Source: University of California – Irvine

Categories : AgeingTags :

‘Feed-forward’ Loop in Cartilage Cells Worsens Osteoarthritis

On By ModernMedia


An unfortunate ‘feed-forward’ loop in cartilage cells appears to exacerbate arthritis, according to researchers Duke University and Washington University in Saint Louis.

Cartilage resists compressive forces, enhances bone resilience, and provides support on bony areas where there is a need for flexibility. In osteoarthritis, the most common form of arthritis,  the cartilage breaks down, allowing painful bone-on-bone contact. Osteoarthritis is the and affects millions of people worldwide with joint pain and stiffness. It is most commonly found in the knees, hips and spine.  

Chondrocytes build and maintain cartilage, with force-sensitive ion channels on their surface, which are called Piezo1 and Piezo2. Piezo channels respond to mechanical loads on the joint by sending signals into the cell that can change gene activity.

In osteoarthritis, degeneration and malfunction of chondrocytes, which are unable to repair themselves by division, contributes to the progressive breakdown of cartilage. Osteoarthritis is als marked by chronic, low-grade inflammation, driven by interleukin-1 alpha, a signalling molecule. Taking cartilage cells from pigs and from human joints removed for replacement surgeries, the researchers investigated the way inflammation affects chondrocytes.

The researchers found that interleukin signaling causes the chondrocytes to produce more Piezo channels, in turn increasing their sensitivity to pressure and resulting in what the researchers term a harmful ‘feed-forward’ loop that leads to further cartilage breakdown.

“Interleukin reprograms the chondrocytes so that they’re more sensitive to mechanical trauma,” Liedtke said. “The feed-forward cycle slowly grinds them down and the cell cannot be replaced.”

Liedtke likened healthy chondrocyte to “a tennis ball”, a bouncy sphere which is kept stiff by its internal matrix of actin fibres. But as these cells lose their ability to replace actin fibres, “they get softer, more squishy.”

However, more Piezo channels were created as the chondrocytes became squishier.

“Overexpressed Piezo channels render the inflamed chondrocyte hypersensitive to mechanical microtrauma, thus increasing the risk of mechanically-induced chondrocyte injury and subsequent progression of osteoarthritis,” said  first and co-corresponding author and biomedical engineer, Whasil Lee, who moved from the Liedtke-Lab to open her own laboratory at the University of Rochester

“It’s cartilage reprogramming itself to do more damage,” Liedtke said.

To confirm this relationship, the researchers blocked the activity of the Piezo channels and observed that the ‘squishiness’ of chondrocytes was reverted.

“We have known that mechanical loading of the joint is essential for maintaining cartilage health,” Guilak said. “In this study, we have uncovered a mechanism by which excessive loading under inflammatory conditions can create a situation that can lead to progressive cartilage degeneration.”

“We’re always looking for feed-forward mechanisms as facilitators of chronic disease,” Liedtke said. “Here we found one, which opens the door for us to come up with disease-modifying treatments, currently non-existent for osteoarthritis.”

Source: Duke University

Journal information: “Inflammatory Signaling Sensitizes Piezo1 Mechanotransduction in Articular Chondrocytes as a Pathogenic Feed-Forward Mechanism in Osteoarthritis,” Whasil Lee, et al. PNAS, March 22, 2021, DOI: 10.1073/pnas.2001611118