Biological complexity: bone body communications (Introduction)

by David Turell , Wednesday, March 09, 2022, 19:36 (990 days ago) @ David Turell

Many, many found:

https://www.smithsonianmag.com/science-nature/how-bones-communicate-with-the-rest-of-th...

"Our bones also provide a handy storage site for calcium and phosphorus, minerals essential for nerves and cells to work properly. And each day their spongy interior, the marrow, churns out hundreds of billions of blood cells — which carry oxygen, fight infections and clot the blood in wounds — as well as other cells that make up cartilage and fat.

"Even that’s not all they do. Over the past couple of decades, scientists have discovered that bones are participants in complex chemical conversations with other parts of the body, including the kidneys and the brain; fat and muscle tissue; and even the microbes in our bellies.

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"Her first finding regarding osteocyte communication with other organs, reported in 2006, was that the cells make a growth factor called FGF23. This molecule then cruises the bloodstream to the kidneys. If the body has too much FGF23 — as happens in an inherited form of rickets — the kidneys release too much phosphorus into urine, and the body starts to run out of the essential mineral. The resulting symptoms include softened bones, weak or stiff muscles, and dental problems.

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"In a 2000 study, Karsenty investigated whether a hormone called leptin could be a link between these two biological processes. Leptin is produced by fat cells and is best known as a depressor of appetite. It also emerged in evolution around the same time as bone. In experiments with mice, Karsenty found that leptin’s effects in the brain put the brakes on bone remodeling.

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"...in 2007, Karsenty proposed that bone also has something to say about how the body uses energy. He found that mice lacking a bone-made protein called osteocalcin had trouble regulating their blood sugar levels.

"In further research, Karsenty discovered that osteocalcin also promotes male fertility via its effects on sex hormone production, improves learning and memory by altering neurotransmitter levels in the brain, and boosts muscle function during exercise. He described these messages

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"For example, skeletal muscle cells make a protein called myostatin that keeps them from growing too large. In experiments with rodents, alongside observations of people, researchers have found that myostatin also keeps bone mass in check.

"During exercise, muscles also make a molecule called beta-aminoisobutyric acid (BAIBA) that influences fat and insulin responses to the increased energy use. Bonewald has found that BAIBA protects osteocytes from dangerous byproducts of cellular metabolism called reactive oxygen species. In young mice that were immobilized — which normally causes atrophy of bone and muscle — providing extra BAIBA kept both bones and muscle healthy.

"In additional studies, Bonewald and colleagues found that another muscle molecule that increases with exercise, irisin, also helps osteocytes to stay alive in culture and promotes bone remodeling in intact animals.

"The conversation isn’t all one-way, either. In return, osteocytes make prostaglandin E2, which promotes muscle growth, on a regular basis. They boost production of this molecular messenger when they experience an increase in the tug from working muscles.

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"The first hints of a bone-microbiome connection came from a 2012 study of mice raised in a sterile environment, without any microbes at all. These animals had fewer bone-destroying osteoclasts, and thus higher bone mass. Giving the mice a full complement of gut microbes restored bone mass to normal, in the short term.

"But the long-term effects were a bit different. The microbes released molecules called short-chain fatty acids that caused the liver and fat cells to make more of a growth factor called IGF-1, which promoted bone growth.

"Gut microbes also appear to moderate another signal that affects bone: parathyroid hormone (PTH), from the parathyroid glands at the base of the neck. PTH regulates both bone production and breakdown. But PTH can only promote bone growth if mice have a gut full of microbes. Specifically, the microbes make a short-chain fatty acid called butyrate that facilitates this particular conversation. (Incidentally, that FGF23 made by osteocytes also acts on the parathyroid glands, tuning down their secretion of PTH.)

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"...what’s clear already is that the skeleton is not just a nice set of mechanical supports. Bones constantly remodel themselves in response to the body’s needs, and they’re in constant communication with other parts of the body. Bone is a busy tissue with broad influence, and it’s working behind the scenes during the most basic daily activities."

Comment: a laundry list of how bones are designed to work with all the other parts of the body. A marvelous example of irreducible complexity.