From Dinosaurs to Astronauts, Long-Live the Bone Cells (Part I)

In what is becoming an annual tradition, this post is the article I submitted to the Wellcome Trust Science Writing Prize 2014*.

When the first vertebrates emerged onto land, their anatomy faced a complex environment. Without the support of water, gravity pulled them towards the earth’s surface. Their source of oxygen went from water, teeming with nutrients, to air, devoid of all but the basics. In response they evolved an incredible skeletal system that allowed for efficient mobility as well as the storage and use of essential minerals. Vertebrates store 99% of the calcium their bodies need ─ to maintain the electrical signals that keep them alive ─ in their bones. You are a vertebrate.

In order to control vital functions, like the release of these minerals from their skeletal storehouse, a complex endocrine system developed. This system consists of primary glands and secondary organs that secrete hormones, signalling the actions that keep your body in balance. A system, it transpires, that seriously involves the skeleton.

Bone is made and maintained by three types of cells: osteoblasts (bone-producers), osteoclasts (bone-removers), and osteocytes. Until recently, osteocytes were thought to be isolated and without function. We could not have been more wrong.

Osteocytes are the most numerous of the three bone cell types, comprising 90-95% of all adult bone cells. While osteoblasts and osteoclasts only live an average of two or three months, osteocytes have an impressively long lifespan of 10─20 years. Residing within bone, they are interconnected by an extensive network and connect to blood vessels, nerves, and other surface-lining cells.

In response to an endocrine factor called parathyroid hormone, osteocytes are stimulated into activating osteoclasts. The osteoclasts break down bone and release the stored minerals into the bloodstream. It is the job of osteoblasts, on the other hand, to replace what is lost with new mineralised bone. This process results in about 10% of the adult skeleton being turned over each year.

What is remarkable though is that in addition to responding to hormones, osteocytes have recently been proven to produce hormones and coordinate their actions with other organs.

The hormone fibroblast growth factor 23 (FGF23) regulates phosphate levels in the body, assisting bone growth, energy storage, and nerve and muscle production. It does this by signalling the kidneys to increase and decrease certain activities. Unusual levels of this hormone are connected to conditions like rickets, bone and muscle wasting syndromes, and tumours such as osteomalacia. FGF23 is almost exclusively produced by osteocytes.

Osteocytes have also been identified as a major producer of osteocalcin ─ a bone-specific protein which acts as a hormone in the body to regulate glucose metabolism. Low levels of osteocalcin can lead to symptoms similar to diabetes like increased fat, irregular blood sugar levels, and insulin resistance.

There is also evidence that osteocytes respond to and produce other essential hormones and proteins ─ and may even play a key role in the manufacture of blood. We are rapidly learning that healthy osteocytes are necessary not only for properly functioning bones, but other organs as well. This makes their deaths all the more concerning.

While osteocytes can live for decades they will eventually die of either old age, damage, or apoptosis (programmed cell death). At birth, less than 1% of osteocytes in our bones are dead, but after the age of 80 this rises to more than 75%. Crucially, osteocytes that undergo death by apoptosis release a protein that recruits osteoclasts to the area. This can lead to increased bone and mineral loss, as it bypasses the parathyroid glands responsible for keeping them in check.

Significantly, bone wasting ─ such as that seen in diseases like osteoporosis, following certain steroid-based medical treatments, when immobilised in hospital beds, and most severely in the zero-gravity environment of space ─ has been shown to increase osteocyte apoptosis.

Astronauts are hyper-aware of the risk of developing weak bones following long-term space missions. Because of it, strict exercise programmes are enforced, which drastically reduce bone wasting. In doing so, astronauts will also have reduced the risk of associated osteocyte apoptosis.

Although not deliberately, considering that osteocytes are proving responsible for regulating more than just our bones, astronauts may actually be preventing or reducing the development of other serious medical problems. This is something the rest of us back on Earth need to consider as our own bones waste away from old age, disease, and inactivity.

Osteocytes have been seen in all vertebrates, from the first jawless fish to dinosaurs like Tyrannosaurus rex. They are present now in us and every other vertebrate on Earth. Perhaps the fact these cells have been conserved throughout evolution should have been an indication that they play an important role beyond simply maintaining bone. It is becoming more obvious every year that the skeleton is not just a structure, it is an organ – and it appears to be orchestrated by the very cell we thought did nothing: the osteocyte.

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*It did not make the short-list and although I was not on the panel of judges (because that would have been a massive conflict of interest, obviously) I have written a little bit about my thoughts on ‘Why I Didn’t Win’.

**Feature image ‘Tyrannosaurus Astronaut’ by Piya Wannachaiwong.