Little Skate, Big Impact
By Farrah Leone
According to the Center for Disease Control USA, over 54 million people, about a quarter of the population are currently living with Arthritis. Athritis is an umbrella term to refer to joint pain or disease. Osteoarthritis is joint pain caused by cartilage between joints wearing down over time. This leaves nerves and bone exposed to rub up against one another.
There’s a solution on the horizon in the paper titled, “Adult chondrogenesis and spontaneous cartilage repair in the skate, Leucoraja erinacea”, that might end this pain for millions of people.
Humans and skates use a lot of the same genes to create cartilage. Leucoraja erinacea (Little Skates) have progenitor cells. Progenitor cell is a type of stem cell (non-specific cell) that eventually will form into a cell specific to different functions of the body. In mammalian cells, stem are programmed to first form as cartilage and then inevitably mineralize into bone over time. I got the opportunity to speak with PhD candidate Aleksandra Marconi about this unusual creature’s ability for medical innovation!
Aleksandra in the lab
How did this research idea come into fruition?
Good question! The idea came into existence long before I even heard about the little skate’s unique potential to help us answer fascinating and challenging biological questions. I could perhaps try to tell you the lovely origin story in my own words, but I believe that such stories are best heard straight from the source. In this case, it is one of the authors of our recent publication and the mind behind it all, Dr. Andrew Gillis – you can read the story told from his perspective on the NODE blog under ‘Conversations with my parents (about adult chondrogenesis and spontaneous cartilage repair in the skate, Leucoraja erinacea). As mentioned in the above blog post, I joined the project during the experimental phase and contributed to the final outcome of our collaboration as one of the investigators.
Do all types of skates have these specific genes that generate cartilage?
Skates, together with sharks and rays, are the only extant vertebrates that possess a cartilaginous skeleton. Although it hasn’t been explicitly tested in other species of skates (and there are about 150 species described!), we have a good understanding that they all share the same genetic machinery necessary for formation of cartilaginous skeleton. In fact, the genes involved in cartilage production in skate were originally identified by studies conducted in more traditional laboratory animal models such as chick, mouse, and zebrafish. These animals, similarly to us, have adult skeletons of mineralised bones and the only cartilage persisting into adulthood is limited to joints.
How genetically similar are humans to skates in other regards?
Humans, other mammals, skates, and cartilaginous fishes (e.g. sharks and rays), belong to the same evolutionary group called jawed vertebrates. As a group derived from the same common ancestor, all of these organisms share a unique set of features that include (but are not limited to) opposing jaws, teeth, and paired appendages. Although cartilaginous fishes do not have a skeleton made of bone, fossil and molecular evidence have indicated that the ancestor of modern sharks once possessed a skeleton made of more mineralised cartilage. This suggests that they have evolved a lighter, cartilage-based endoskeleton from a bony precursor.
In summary, we are quite similar to skates in many aspects of our biology. If we look beyond numerical answers to your question, the products of these genes perform similar functions during embryonic development and adult life. In that aspect we are quite similar to skates.
What is the difference between metapterygium cartilage and other forms of cartilage?
One of the main reasons we use metapterygium in our studies is due to the practical reasons: it is a large element of the skeletal system and it is easily identifiable as well as accessed e.g. for the injury experiments. However, most of the cartilages of the skate skeleton are made of hyaline cartilage – a type of cartilage that consists of cartilage cells called chondrocytes and a distinct type of secreted matrix, and that is similar to the type of cartilage that is typically found in joints in mammals, including humans
How do you see this research being used to advance medical care? Do you see it as a possibility for some type of medication, injection, treatment, etc?
As researchers in fundamental or basic science, we are asked these kinds of questions a lot. Luckily, in this case, we can firmly say that our research, at some point in the future, might actually lead to advancements in medical care. The next step now is to explore and understand how the specialised ‘skate cartilage stem cells’ identified in our experiments are able to generate cartilage as a stable tissue of the adult skate skeleton. This, eventually, could lead to a possible application to human stem cells, where these cells would be induced to mimic the behaviour of their counterparts in skate, enhancing their ability to produce lasting cartilage that could be used in novel therapeutic strategies to mitigate conditions such as osteoarthritis, by repairing or replacing the damaged cartilage.
What advice do you have for women of all ages that want to get involved in marine based STEM?
I believe that passion about the subject is already a half of the success. Akin to the ocean itself, there are lots of exciting opportunities out there – but you might need a healthy dose of enthusiasm and determination to see your ideas come to fruition. Even though these fields remain to be male-dominated, it does not mean that we should be intimidated. The success stemming from true passion and resilience in the face of adverse circumstances tastes the sweetest.
