According to Newton, “For every action, there is an equal and opposite reaction”—a concept familiar to anyone who has ever played tug-of-war. But even a couch potato faces a constant bombardment of mechanical stress, from the daily necessities of physical activity to the unavoidable pressures of gravity. This stress affects skeletal tissue, triggering bone growth or bone loss as the body tries to maintain structural equilibrium. While this effect on skeletal development has long been noted, scientists are still trying to unravel the molecular response to these outside forces.
Researchers in the lab of Bjorn Olsen, dean of research and professor in the Department of Developmental Biology at HSDM, have uncovered one piece of this puzzle. Reporting in the June 2009 issue of Bone, they describe how a gene called Pkd1 contributes to the body’s response to mechanical stress.
The researchers gently stretched the palates of mice using midpalatal suture expansion, a process that triggers measurable new bone formation. Since mice deficient in the Pkd1 protein PC1 were already shown to have difficulty with bone development, the researchers used the technique to test Pkd1’s involvement in the body’s response to mechanical stress.
The researchers measured new bone formation in four groups of mice. The first group had normal Pkd1 activity while the others had Pkd1 deleted in selected cells. The team found that when Pkd1 was suppressed in neural crest cells—progenitor cells that give rise to bone and cartilage—the mice lacked the expected bone formation exhibited by the control and other Pkd1-deleted groups.
“The findings show that Pkd1 is clearly important to the progenitor cells’ ability to respond to mechanical stress,” said first author, Bo Hou, a former PhD student in the Olsen lab and a resident in orthodontics and dentofacial orthopedics at Tufts School of Dental Medicine. “We think PC1 may act as a mechanical sensor, helping to initiate bone tissue activity in response to mechanical stress, though more studies are needed to confirm this.”
This study establishes midpalatal suture expansion as a method for testing the genetics of bone development, with implications for skeletal diseases such as osteoporosis and osteoarthritis, as well as orthodontic and orthopedic treatments.
“If we can understand the process better,” Hou explained, “we could develop improved strategies to manage these kinds of cases, which would be good news for the patient and for our healthcare system.”
Students may contact Bjorn Olsen at bjorn_olsen@hms.harvard.edu for more information.
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