11 August 2014
By Isabel Quiros-Gonzalez
Nearly 15 years ago, in a class during the first year of my degree, the professor of histology was explaining bone tissue. He described the main types of cell within bone, and I remember feeling underwhelmed by osteocytes, a cell that becomes trapped in the bone it has just built. I thought to myself, “What cell is stupid enough to get trapped in its own house and rendered useless?”
Years later, I discovered the answer to that question: there is no such cell. Osteocytes are quasi-bone neurons, able to detect the mechanical loads on the body and make the bone harder or softer in response. This was the first, but not the last time that discoveries in bone biology over the past 20 years have amazed me.
For many years, bone has been considered by me and many other researchers to be a static structure that holds and protects the soft tissues of the body and provides the body with its main store of calcium. I have also known that bone is strongly regulated by serum calcium levels, vitamin D, oestrogen, growth hormones and parathyroid hormones. This, for a long time, has been the extent of my knowledge.
But then, in early 2000, we began to see bone differently; for the first time it was reported that signals from the brain caused by leptin, an appetite hormone, caused a decrease in the calcium content of bones. Findings in this first study were later confirmed by others, and today, the connection between the brain and bones is still an exciting field of research.
Many neurotransmitters and molecules produced in the brain have now been described as bone regulators:
- Adrenalin, produced in a part of the brain called the hypothalamus, can reduce bone mass.
- Serotonin, produced in another part of the brain called the brain stem, can increase bone mass by inhibiting adrenalin signalling.
- Neuropeptide Y, also produced in the hypothalamus, has a complex dual regulation of bone by either using the central nervous system or targeting the bone directly.
- In addition, many other neurotransmitters and brain-derived molecules like POMC, CART or BDNF are being studied.
And then there’s a second level control that the brain exerts on bones: the pituitary gland, also found in the brain, produces and secretes a number of hormones that affect bones directly, including Growth Hormone (GH), Follicle Stimulating Hormone (FSH) and Thyroid Stimulating Hormone (TSH). These hormones travel in the blood and target bone and other organs, including the liver, sexual organs and the thyroid gland.
These organs, when stimulated by GH, FSH and TSH, will produce other hormones that also affect bone, for example the growth hormone Insulin-like Growth Factor 1 (Igf-1), sexual hormones such as oestrogens and androgens and thyroid hormones such as T3 and T4. This string of complex interactions and pathways are, in one way or another, regulated by the brain. (See figure above.)
Today at the Sanger Institute, we try to find the causes that underlie bone alterations and bone diseases, by studying alterations in these pathways. For me, all these new pathways provide a new perspective from which to look at bones, like studying them with new eyes. Imagine you have to represent a bird but you can only paint it. You can paint it many times but you will still only see one side. Then imagine carving a sculpture of a bird; this allows you to see it from many angles at the same time. This new perspective is what we are hoping to achieve when we look at bones and how they interact with the brain and the rest of the body.
Isabel Quiros-Gonzalez is Visiting Scientist at Sanger Institute with the ERA-EDTA postdoctoral fellowship program. She works under the supervision of Vijay Yadav, studying the mechanisms that underlie bone loss in ageing.
- Quiros-Gonzalez, et al (2014). Central genes, pathways and modules that regulate bone mass. Archives of Biochemistry and Biophysics. DOI: 10.1016/j.abb.2014.06.005