|Scanning electron micrograph of an osteocyte in resin. Click on the image to see in full resolution. Image credit: Lynda Bonewald
Lots more to do
Experts interviewed for this story were unified in their upbeat enthusiasm for the future of molecular biology research into bone simply because there are so many rich hunting grounds in both basic and clinical endeavors. Experts are unrestrained in their enthusiasm when they say that new anabolic drugs will be developed in the next decade to help patients with postmenopausal, age- or disease-induced osteoporosis and skeletal fragility.
For basic researchers, there are many directions to pursue. For one, they need to understand how bone cells communicate and respond to mechanical and biochemical signals both at local and systemic levels. For example, “bone is an incredibly locally focused tissue,” says Kronenberg. “If you break a leg, you want to fix that fracture right where it is. You don’t want a systemic response to a fracture.” How bone senses when to work locally and when to act globally is a question.
Another interesting idea that is emerging is that there is two-way communication between muscle and bone. “We always think of muscle affecting the skeleton” by pulling and pushing on the bones, says Rosen. “But there’s the converse side: How does the skeleton regulate muscle?”
This is work Bonewald has undertaken in collaboration with the groups of Marco Brotto and Mark Johnson, also at the University of Missouri in Kansas City. “We took some of our osteocyte-conditioned media and put it on muscle cells. [Brotto] was absolutely blown away to see that the osteocytes secrete factors that support myogenesis,” Bonewald says. “If you put the conditioned media on intact muscles that are contracting, it increases muscle force.” She says the collaborators are working on figuring out the factors secreted by the osteocytes and how they affect signal-transduction pathways in muscle.
Indeed, factors secreted by bones are high on the exploration list. This is especially true for the relatively new discovery that bone senses and possibly influences metabolism. In Rosen’s opinion, “the skeleton is secreting lots of endocrine factors. We know about FGF23, sclerostin and osteocalcin. We don’t know enough about those, and my guess is there are also other substances being produced.”
As schoolchildren, our earliest encounters with bone are with the jangling skeleton hanging in the back of the high-school biology laboratory. But with new findings emerging about the inner workings of the skeleton, bones can no longer be viewed as stiff and inert structures that simply hold us upright. Bone is truly a dynamic, living tissue that is constantly listening and responding to the way we live.