Manipulating Cellular Communication in Cartilage to Treat Osteoarthritis
Osteoarthritis is a joint disease where the cartilage—the flexible tissue that protects the ends of bones—gets worn down, causing the bones to grind rather than slide against each other during movement. This results in difficulty moving and completing simple tasks, painful aches, and stiffness in several areas, especially in the knees, hips, lower back, and neck. Currently, it is the most common disorder in the United States. Osteoarthritis affects 10% of women and 13% of men 60 and older, and the percentages only increase with age. Although over-the-counter pain medication and surgeries may provide some relief, there is currently no specific treatment plan or cure.
Scientist Yulong Wei and his team of researchers sought to solve this issue by examining an epidermal growth factor protein (EGF) cell signaling pathway in mice. EGFs are a type of protein that controls when cells grow and divide and are only activated when bound to a specific receptor, known as an epidermal growth factor protein receptor (EGFR). Because humans share 81% gene sequence similarity to the same signaling pathway in mice, mice are a suitable species for research to compare to humans. The researchers detected that mice with low levels of EGFR also had weaker cartilage structures and decreased bone cell production, thus being more likely to develop arthritis over time.
Scientist Yulong Wei and his team of researchers sought to solve this issue by examining an epidermal growth factor protein (EGF) cell signaling pathway in mice. EGFs are a type of protein that controls when cells grow and divide and are only activated when bound to a specific receptor, known as an epidermal growth factor protein receptor (EGFR). Because humans share 81% gene sequence similarity to the same signaling pathway in mice, mice are a suitable species for research to compare to humans. The researchers detected that mice with low levels of EGFR also had weaker cartilage structures and decreased bone cell production, thus being more likely to develop arthritis over time.
Therefore, the researchers thought that by increasing EGFR signaling, they could reduce the likelihood that the mice would develop arthritis. To test their assumption, they first took three different categories of mice with varying genes that overexpressed an EGF protein, called heparin-binding EGF-like growth factor protein (HBEGF), in cartilage and bred many of them together. This allowed the researchers to study what would happen when too much of the overexpressed protein binds to the EGF receptor protein in cartilage. In the second stage of the experiment, the researchers delivered a signal in the knee cartilage that would increase growth factor signaling further by adding another protein known as transforming growth factor alpha (TFGA). TFGA is a molecule, or a ligand, that would bind to the EGF protein and increase cellular growth further.
The researchers found that mice with the genes that overexpressed the growth factor protein HBEGF had more bone cells and thicker cartilage in comparison to standard mice. This was most evident when the mice were one month old and had a 16% increase in the growth plate, and at 5 months old where they had a 23-34% increase in cartilage thickness. In addition, the joints appeared to be unaffected. This is noteworthy since if a similar treatment would be designed for humans, it would be ideal for the joints to not consequently bulge. The treated mice also experienced an increase in the chondroprogenitor pool, a gene type responsible for cartilage development.
In the third stage, the scientists performed surgery on the mice, where they destabilized their medial meniscus, one of the bands of cartilage attached to the shinbone that stabilizes the knee. They then injected the mice with TFGA, the previously discussed signaling molecule that was suspected to increase cellular growth. The mice who received the injections post-surgery had less degeneration in their cartilage than those without it. The process also did not damage vital organs.
Overall, although the research conducted in mice may not be completely representative of how it may affect humans, the experiment is promising. The results highlight the potential of manipulating cellular communication pathways and genetics to increase the amount of cartilage in an organism. As a result, further research on these techniques could potentially lead to the development of drugs or therapeutics to treat arthritis and other cartilage disorders.
The researchers found that mice with the genes that overexpressed the growth factor protein HBEGF had more bone cells and thicker cartilage in comparison to standard mice. This was most evident when the mice were one month old and had a 16% increase in the growth plate, and at 5 months old where they had a 23-34% increase in cartilage thickness. In addition, the joints appeared to be unaffected. This is noteworthy since if a similar treatment would be designed for humans, it would be ideal for the joints to not consequently bulge. The treated mice also experienced an increase in the chondroprogenitor pool, a gene type responsible for cartilage development.
In the third stage, the scientists performed surgery on the mice, where they destabilized their medial meniscus, one of the bands of cartilage attached to the shinbone that stabilizes the knee. They then injected the mice with TFGA, the previously discussed signaling molecule that was suspected to increase cellular growth. The mice who received the injections post-surgery had less degeneration in their cartilage than those without it. The process also did not damage vital organs.
Overall, although the research conducted in mice may not be completely representative of how it may affect humans, the experiment is promising. The results highlight the potential of manipulating cellular communication pathways and genetics to increase the amount of cartilage in an organism. As a result, further research on these techniques could potentially lead to the development of drugs or therapeutics to treat arthritis and other cartilage disorders.
Featured Image Source: Karolina Grabowska
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