Bone adaptation and mechanotransduction; Fluid and mass transport in biological systems; drug delivery; Cellular Imaging; Mathematical / Numerical Modeling
As a living tissue, bone keeps changing its structure and mass to meet the requirements of its chemical, hormonal, and mechanical environments. This phenomenon is called bone adaptation. Good examples are the larger and stronger arms that professional tennis players use to play compared to their contralateral arms, rapid bone loss for astronauts in space, as well as osteoporosis in women after menopause. Although these phenomena are well documented, the cellular mechanisms involved in bone adaptation and its ability to sense its external mechanical stimuli are not well understood. The long-term goals of my research are 1) to understand the cellular mechanisms of bone mechanotransduction using an integrated multi-disciplinary approach such as imaging techniques, mathematical / computational modeling, and animal models; and 2) to develop intervention schemes to treat various bone conditions and diseases.
Our current research focuses on fluid and solute transport in bone. Osteocytes, the most numerous cells in bone, are critical for bone health and bone quality. These star-like cells form an interconnected network among themselves and also with other bone cells lining bone surfaces (Fig. 1). They function as sensor cells to detect external mechanical stimuli and to pass the information to other bone cells responsible for new bone formation (osteoblasts) and removal of existing bone (osteoclasts). Since osteocytes are completely encased in mineralized bone matrix, their survival and function are entirely dependent on transport of solutes (metabolites, growth factors, cytokines, and other signaling molecules) through the interconnected pore system around their cell bodies and long protrusions (termed lacunar-canalicular system, Fig. 1). Despite advances in delineating transport pathways in bone, little is known about the mechanisms involved in moving biological molecules to and from osteocytes in vivo.
Several projects are being undertaken in my laboratory (1) to investigate how solute diffusion and convection are modulated by the ultrastructures of the fluid pathway and mechanical stimuli in normal and diseased bones; (2) to examine genetic influences on solute transport in inbred mice; (3) to explore mass transport enhancement methods for drug delivery applications in the skeletal system. These studies will delineate the transport mechanisms that are essential for osteocyte viability and bone mechano-transduction, and provide new insights into mass transport in other biological and engineered systems (e.g., tissue engineering scaffolds). Detailed knowledge of how molecules move within bone will help define molecular parameters such as hydrodynamic radii and half-life times for new drugs so that they can be delivered effectively into bone to treat diseases such as osteoporosis and arthritis.