Our skeletons do more than just hold us upright
Do what you love. Know your own bone; gnaw at it, bury it, unearth it, and gnaw it still.
— Henry David Thoreau
Most of us appreciate that if it weren’t for our skeletons, we’d be bags of protoplasm oozing on the ground. But beyond that, a common perception of bone is that it’s simply an inert mineralized tissue that does only a few things: protect delicate organs, help us to walk, act as a mineral store and house the blood-making machinery.
But that perception has started to shift over the past two decades. Thanks to advances in cellular and molecular biology tools, experts now say that bone is a dynamic tissue that sends out and receives messages from organs. It even tweaks the functions of organs and actively participates in maintaining mineral and energy homeostasis throughout the body.
Old to new
Bone constantly turns over. This process is called bone remodeling and rebuilds the skeleton bit by bit. Bone remodeling is the reason you don’t have the same skeleton today as you did 10 or so years ago.
Understanding how bone remodeling happens at the cellular and molecular levels was a challenge for decades because the mineralized matrix of bone, containing calcium and phosphate, had made culturing bone cells by conventional methods difficult. But now a clearer picture is starting to come into focus. There are thought to be three types of bone cells: osteoblasts, osteoclasts and osteocytes. Osteoblasts build bone by putting down the mineralized matrix. Osteoclasts chew down bone. They are unique in that they are the only cells in the body designed to destroy their host tissue. Both cell types sit on the surface of the bone.
The challenge of studying bone is most evident when it comes to the osteocytes, cells derived from osteoblasts that make up 90 percent of bone. Because they sit deep inside the bone, studying them had been especially hard, and the difficulty led a number of researchers to ignore the cells. As Henry Kronenberg at the Massachusetts General Hospital quips, the conventional thinking used to be that osteocytes were just “stupid osteoblasts that got buried and stuck in bone.”
Lynda Bonewald at the University of Missouri in Kansas City, an immunologist and hematologist by training, became intrigued by the osteocytes inside the bone matrix in the late 1980s because of their striking resemblance to neurons with dendritic protrusions. When she asked experts in the bone field what osteocytes did, “I was told they were just placeholders,” she says. “I couldn’t accept that explanation. I started thinking of ways to make cell lines.” Starting in 1997, Bonewald’s group began to report osteocyte lines, such as MLO-Y4, which gave researchers a better idea of what the cells actually do. Osteocytes act as the mechanosensors of bone, probably sensing changes in fluid flow and how the skeleton is weighted during rest or exercise, a hypothesis Bonewald says histomorphologists proposed decades ago. She says osteocytes are probably not important as mechanosensors in the embryonic skeleton or very active postnatally during growth. But they are extremely important in adults. Osteocytes direct osteoclasts and osteoblasts where to degrade old bone and set down new material. They also secrete hormones. “Instead of being thought of as pitiful cells that got confused and stuck inside bone, they are now thought of as the master cells,” says Kronenberg. “They are the brains of the outfit.”