Osteocyte spindles responsible for sensing mechanical stimulation, signaling bone growth

Investigators from Texas have discovered a key factor in the process of bone remodeling and report that their findings could possibly lead to new treatments for osteoporosis, osteoarthritis and age-related bone loss.

Sirisha Burra, PhD, from the University of Texas Health Science Center at San Antonio, Tex., and colleagues, found that the spindly extensions of bone cells — dendrites — are responsible for sensing mechanical stimulation and signaling the release of bone growth factors, according to a press release.

“Maintenance of bone health depends on the osteocytes’ ability to sense the stimulation,” Burra stated in the release. “If osteocytes lose this ability, it could possibly lead to diseases such as osteoporosis. Hence, it is important to understand this mechanism.”

Mechanical impact and stress

The investigators estimated the mechanical impact of force applied to the dendrites and determined the magnitudes of mechanical stress, according to the release.

“Understanding how bone cells sense and respond to mechanical signals within the skeleton is an inherently multidisciplinary problem,” co-author Daniel P. Nicolella, PhD, institute engineer in the Mechanics and Materials Section at Southwest Research Institute, stated in the release. “We determined the mechanical stresses applied to the osteocytes in these experiments so that they can be compared to the mechanical signals predicted to occur within the skeleton during routine physical activities.”

To determine which part of the osteocyte — the cell body or the dendrites — acts as a mechanical sensor, the authors applied mechanical loading to the individual parts of the cell. The hemichannels located on the cell body were induced to open when mechanical loading was applied to either the cell body or the dendrites, according to the study abstract.

Effects of mechanical loading

No significant hemichannel activity was detected in the dendrites when either part of the cell was mechanically stimulated, Burra and colleagues reported. Disruption of the glycocalyx by hyaluronidase on the dendrite side diminished the dendrite’s ability to induce hemichannel opening on the cell body, while hyaluronidase had no such effect when applied to the cell body. Hyaluronidase applied to the dendrite side resulted in poor integrin attachments with the reduced ability of the dendrites to form integrin attachments on the underside of the transwell filter.

“Together, our study suggests that the glycocalyx of the osteocyte dendritic process is required for forming strong integrin attachments,” the authors concluded. “These integrin attachments probably serve as the mechanotransducers that transmit the mechanical signals to the cell body leading to the opening of hemichannels, which permits rapid exchange of factors important for bone remodeling.”

The study demonstrated that different parts of a single cell can have different material and sensory properties and can react differently to the same stimulus. “This is a very important fact to consider while studying cellular signaling and regulatory mechanisms,” Jean Jiang, PhD, senior corresponding author, stated in the release.

Reference:
Burra S, Nicolella DP, Rrancis WL, et al. Dendritic processes of osteocytes are mechanotransducers that induce the opening of hemichannels. Proc Natl Acad Sci USA. doi:10.1073/pnas.1009382107.