The importance of bones for us cannot be overstated. They keep our bodies upright, protect our internal organs, allow us to move our limbs, and support our bodies instead of piling up on the ground. When we’re young, bones grow with us and recover easily from fractures. However, with age, bones will become more and more fragile and often damaged, broken, even need surgery to replace.
The structural functions of bone are inherently rich, but its role is much more. Our bones also store large amounts of calcium, phosphorus, and minerals, which are important for nerve and cell function. In addition, bone marrow produces hundreds of billions of blood cells each day, which are used to transport oxygen, fight infection, clot bleeding wounds, and other cells that make up cartilage and fatty tissue.
And that’s still not enough. In recent decades, scientists have discovered that bones are also involved in complex chemical exchanges with other parts of the body, including the kidneys, brain, adipose tissue, muscle, and even the gut flora. It’s as if you suddenly discovered that the beams and joists in your home can communicate with the air conditioner, refrigerator, microwave… Scientists are also deciphering how bone cells send signals signals to other organs and how they interpret and respond to foreign molecular information. Clinical scientists are thinking about how to use this cell communication to develop new ways to protect or strengthen bones.
This is a whole new area of exploration, and recent studies have led scientists to realize that bones are much more dynamic than previously thought.
Bone is a unique “organization” that not only contains cells that give strength, but also cells that decay, allowing bone to continue to grow during childhood and to regenerate broken bone throughout life. The cells responsible for building bone are called osteoblasts, and the cells responsible for breaking them down are called osteoclasts. When these two types of cells work out of balance, the body can make too little (or too much) bone. For example, osteoporosis occurs when new bone does not form as quickly as old bone degenerates, so the bones become loose and brittle.
In addition to osteoblasts and osteoclasts, bone contains another type of cell called osteocytes. Although these cells make up more than 90% of the total cells in bone, they have not been studied in depth. It wasn’t until 20 years ago that a cell biologist named Lynda Bonewald working at Indiana University in Indianapolis became interested in it. Her colleagues advise her not to waste her time, because bone cells may be nothing more than their normal function of sensing mechanical force and regulating bone remodeling.
But Bonewald decided to take a closer look. She and other researchers found that bone cells actually sense mechanical loads. But she also points out: “It’s much more than that.”
She writes about the importance of bone cells for the kidneys, pancreas and muscles, in 2006 she published the first report on the communication of bone cells with other organs, in which indicates that the bone cells make a growth factor called FGF23.
This molecule travels through the bloodstream to the kidneys. If there is too much FGF23 in the body – as occurs in an inherited form of rickets – the kidneys release too much phosphorus into the urine, causing the body to lose this essential mineral, causing rickets and muscle weakness or stiffness and dental problems.
Around the same time Bonewald was studying bone cells, physiologist Gerard Karsenty also began investigating the relationship between bone remodeling and energy metabolism. He speculates that there may be a connection between the two, since the destruction and rebuilding of bone is an energy-intensive process.
In a 2000 study, Karsenty analyzed the link between a hormone called leptin and both of these biological processes. Leptin is produced by fat cells and its main role is to suppress appetite. In evolution, it appeared at the same time as bone. And Karsenty found in experiments on mice that leptin affects the brain, stopping bone remodeling.
In this way, bony organisms can initially suppress appetite and bone growth in the absence of food and save their energy for daily functions.
The team used X-rays to scan the hands and wrists of several children with a lack of fat cells (and thus a lack of leptin) due to a genetic mutation. According to the radiologist, the bone age of these children is several months or even years older than their actual age. This suggests that in the absence of leptin, their bones grow faster, reflecting characteristics of older bones such as higher bone density.
It was a case of bones listening to other organs, but in 2007 Karsenty suggested that bones also say something about how the body uses energy. He found that mice lacking a bone-building protein called osteocalcin had trouble regulating their blood sugar.
In further research, Karsenty discovered that osteocalcin also promotes male fertility through its effects on sex hormone production, improving learning and memory by altering levels of neurotransmitters in the brain, and enhanced muscle function during exercise. He described these messages, and other “conversations,” in which bones engage, in the 2012 Annual Review of Physiology.
Whether or not osteocalcin played an important role in vertebrate evolution, these studies have inspired other scientists to begin studying how bones communicate with organs. other body.
During the movement of the body, bones and muscles are a “partner”, participating in various physical interactions. The muscles pull on the bone, and as the muscle grows larger and stronger, the bone also gets bigger and stronger to resist the increased pulling force of the muscle. In this way, the bones will adapt to the body’s needs so that the bones and muscles always work together effectively.
But scientists have discovered that there is also metabolism between these two “partners”. For example, skeletal muscle cells make a protein called myostatin, which prevents muscles from growing too large. Simultaneously in rodent experiments and human observations, the substance also inhibited the growth of bone mass.
During exercise, muscles also synthesize a molecule called beta-aminoisobutyric acid (BAIBA), which affects how fat and insulin respond to increased energy expenditure. Bonewald also found that the molecule can reduce damage to bone cells by reactive oxygen species, a byproduct of cellular metabolism. In young mice immobilized for a long time, they experienced bone and muscle atrophy, but when beta-aminoisobutyric acid was added, their muscles and bones gradually returned to normal.
In further study, Bonewald and his colleagues also found another molecule, irisin, increased with exercise. When cultured in a test tube, this substance helps bone resorption cells stay active; and in animals, the molecule also promotes bone regeneration.
Moreover, this communication is not overnight. In turn, bone cells regularly produce prostaglandin E2, which promotes muscle growth. The secretion of this molecule is increased when the bones perceive increased muscle tension.
Our bodies contain almost equal numbers of cells and microorganisms. The gut colony is like another organ and plays a certain role in the body. They help us digest food, prevent infections caused by harmful bacteria, and communicate with other organs, including bones.
So far, communication between bone and the gut microbiome appears to be one-way. No one has yet observed that bone transmits information to the gut microbiome, but bones can pick up a lot of useful information from the gut. For example, in the case of severe food poisoning, when we need to use all of our body’s resources to fight an infection, this is not the best time for bone growth.
The link between bone and the microbiome was first seen in a 2012 study. The mice used in this study were all raised in a sterile environment without any microorganisms. in their body. They have fewer osteoclasts in the body and therefore more bone mass. When these mice were supplemented with gut bacteria, their bone mass quickly returned to normal levels in a short time.
The most exciting thing about these findings is that they could help us find new ways to treat bones, allowing drugs to work in different parts of the body.
It is estimated that nearly 13% of people over the age of 50 have osteoporosis, and while drugs that can slow bone breakdown or promote bone growth have side effects and are less effective. So we need to find a new treatment.
We can start with the gut first. Probiotics, as well as foods containing purposefully cultured bacteria, such as fermented dairy products, can help build a healthy gut microbiome. Lactobacillus reuteri can help mice fight bone loss after antibiotic treatment.
Scientists still have a lot to learn about communication between bones and other parts of the body. Over time, these studies could lead to more treatments to keep bones and other body parts healthy.