Mechanobiology

Mechanobiology merges the older science of mechanics with the newer and emerging disciplines of molecular biology and genetics. At the center of mechanobiology is the cellular process of mechanotransduction, or the way cells sense and respond to mechanical forces. Many, if not most, of the tissues in the body contain mechanosensitive cells. These include osteocytes in bone, chondrocytes in cartilage, myocytes in the heart, endothelial cells in blood vessels, epithelial cells in renal tubules, and many others. Of the five senses defined by Aristotle - sight, hearing, taste, smell and touch - two require cellular mechanotransduction. In addition what is often called the sixth sense, our sense of space and location called proprioception, relies on mechanosensors as does the sense of balance. There are many clinical applications of mechanobiology, including orthodontic tooth movement, distraction osteogenesis, artery stents, artificial heart valves, as well as promising new treatments for diabetes, muscular dystrophy and osteoporosis. Another use of mechanobiology is the development of new pain killers. Many pain sensing nociceptors are in fact mechanosensors that detect local tissue deformation and send signals to the brain that are perceived as pain. Blockers of mechanotransduction in nociceptors show promise for treatment of chronic pain syndromes.

Our work focuses on mechanotransduction in bone tissue. Exercise causes bones to increase bone mass and strength. More importantly the mechano-sensing apparatus in bone directs new bone formation to where it is most needed for improving bone strength. We are working to identify the key features of the bone mechano-sensory apparatus. We have established three major rules for mechanosensation in bone and are working to identify the molecular events involved. These include autocrine and paracrine signaling and several key transcriptional pathways that activate bone matrix synthesis. Download our articles for more about the mechanisms of bone strength and the molecular pathways involved in mechanotransduction.

Recent studies have uncovered mechanisms by which exercise affects muscles and bones. Aerobic exercise improves oxygen delivery to skeletal muscle and increases the ability of muscle to burn carbohydrates and fatty acids. These effects can be replicated by drugs that activate a transcription factor called PPARd. Suppression of a protein called myostatin increases muscle mass and strength, similar to strength training. Activation of signaling in the Wnt pathway can strengthen bones similar to what would be expected with rigorous exercise. These findings pave the way to new ways to treat chronic diseases like diabetes and osteoporosis and may allow the development of medical treatments that provide some of the beneficial effects of exercise. For more on the exercise pill, click here.

Increased muscle mass in the myostatin knockout mouse (right).
from McPherron and Lee. Nature. 1997;387;83-90

Increased bone density in person with high bone mass
(HBM). This results from excessive Wnt signaling
through the LRP5 receptor.
Courtesy of Robert R. Recker, Creighton University

We have shown that mechanical loading strengthens bones through the Wnt signaling pathway, and the key receptor in this process is low-density lipoprotein receptor-related protein 5 or Lrp5. If Lrp5 is made non-functional in mice by genetic engineering the bones are no longer sensitive to mechanical loading. Download our article on Lrp5 here.