Cartilage as Rejuvenation

I have studied cartilage secreting (chondrocytes) for the last few years. Chondrocytes are normally derived by differentiation of mesenchymal stem cells (MSCs) that grow in the bone marrow. MSCs can differentiate to produce bone secreting cells (osteoblasts), muscle cells (myoctes), fat cells (adipocytes) and insulin-secreting cells (beta-pancreatic islet cells.) I chose to study a rat chondrosarcoma (RCS) cell line, because this is a type of cell that shares the properties of many other important cells and it will continue to grow in cell culture. Thus, I can dilute some RCS cells in a solution with all of the nutrients required for growth and the cells will stick to the surface of the plastic dishes that I use, grow and differentiate. If you stain the cultures for cartilage, you get the following micrograph.

At first the cells stretch out and move about the surface of the dish. Then they become progressively less adhesive to the surface and more spherical as they start to produce and secrete the polysaccharides (glycosaminoglycans, such as chondroitin sulfate and heparan sulfate) and proteins (collagen) of cartilage. Finally they produce thick layers of cells that are separated and embedded in cartilage. After a little more than a week in culture, the cells are moving through the cartilage matrix by enzymatically degrading the cartilage ahead of them and secreting new cartilage in their wake. The cells that eat their way to the dish surface separate the cartilage layer from the dish and the colonies of cells begin to slough off from the dish surface. Normal chondrocytes would eventually stop dividing under culture conditions, but the cancer line that I use continues to grow quite happily and can be diluted and plated continuously. Chondrocytes in cartilage live in cavities within the cartilage and are surrounded by heparan sulfate attached to proteins of their cell membranes, i.e. heparan sulfate proteoglycans.

Cut cartilage will grow back together as the chondrocytes mine, secrete and gradually knit the two surfaces together with strands of new cartilage. Movement through and renewal of cartilage, e.g. in the connective tissue of skin, is restricted if the collagen fibers that are assembled outside of the secreting cells are cross-linked. This is why sunbathing ages skin. High fructose corn syrup also accelerates cross-linking. This cross-linking is also what makes meat less tender. The cross-linking and toughness can be measured by inserting fluorescence-measuring probes into meat, because the protein cross-links fluoresce in UV light.

A consequence of the development of chondrocytes on the ends of bones, is that the nutrients for the cells change. Initially the chondrocytes enjoy the abundant glucose and oxygen of the blood stream and gradually they are remove further from blood vessels. (Note that cartilage actively inhibits vascularization, so there are no blood vessels in cartilage. This lack of blood vessels and associated enhanced risk of disfiguring infection, is a reason to discourage piercings that involve cartilage.) Chondrocytes snug in their little cartilage cavities no longer eat sugar or breath oxygen, they dine on cartilage and ferment.

What happens if you expose mature chondrocytes to a new source of rich nutrients? I think that the answer is rejuvenation. Quite literally, the chondrocytes regress and return to the lifestyle of their youth. Instead of producing mature, weight-bearing, dense cartilage, these rejuvenated cells start to produce the weaker matrix of their youth. This weak cartilage is readily damaged by abrasion and is not suitable for joint surfaces. This is one of the consequences of arthritis. Inflammation of cartilage brings rejuvenating, damaging nutrients to chondrocytes. The mechanical damage leads to destructive cycles of further inflammation.

Chondrocytes in cartilage also respond to mechanical stress and this stress maintains their maturity. Persistent weight bearing at the same orientation leads to bone production. Thus, after joint injury it is important to use the correct regimen of rehabilitation to maintain mobility of the joint and mineralization of the bone.