Bone Cell Viability: Is Physical Activity the Key?
The Cleveland Clinic Musculoskeletal Research Center Mechanobiology Laboratory is establishing a biophysical basis for mechanotransduction in bone, providing unique insight into the biology underlying processes associated with bone growth, adaptation and repair. Once such basic mechanisms are elucidated, the development of new treatment modalities for acute or chronic problems, such as fracture, osteoporosis and osteomyelitis, will be possible.
Using innovative methods in an ex vivo sheep model, an in vivo rat model and an in vitro model using bone explants, Mechanobiology Laboratory researchers have proven the postulate that mechanical loading drives fluid flow through bone. Furthermore, they have shown that fluid movement resulting from mechanical loading enhances molecular transport from the blood supply to the osteocytes, thus playing an important role in osteocyte viability. This has tremendous clinical implications for healing bones.
In addition, the mechanobiology research team has developed theoretical computer models to predict flow patterns under simulated model conditions. By comparing the predictions of such models with actual experimental results, we have begun to explicate the relationship between mechanical loading parameters and fluid dynamics in bone. Such parallel studies have been important for understanding, for example, the role of fluid flow in the hypertrophic response of rats to four-point-bending loads.
Furthermore, we are able to link spatial information such as local architecture to distribution of flow and to osteocyte signaling. Recent studies showing the distinct molecular sieving properties of bone implicate a role of mechanical load-induced fluid flow in modulating the distribution of cytokines through the tissue.
These effects are observable in soft tissues of the musculoskeletal system as well. Interestingly, not only strenuous exercise but also normal daily activities promote transport of nutrients and growth factors through bone.
In summary, we are forming a global picture of fluid flow that has tremendous implications for cell viability, cell integrity, as well as the governance of functional adaptation and repair within bone tissue.
(Above)Osteocytes are connected to each other, to bone surfaces upon which osteoblasts rest, as well as to the blood supply via canaliculi. These small canals, through which the cell processes protrude, provide an exquisite network for intra- and extracellular traffic.
In healthy cancellous bone (top), fluid flows from the blood supply of the marrow space through the lacunocanalicular network to osteocytes remote to the blood supply. After endoprosthesis implantation (bottom), lack of mechanical loading as well as disruption to the blood supply adversely affect fluid flow through cancellous bone, impairing osteocyte viability and threatening tissue survival.
