The focus of my lab is in the areas of mechanobiology/bioengineering of cartilage and bone. Briefly, we are involved in the fundamental research and translational studies through:
Comprehensive understanding of the mechanotransduction pathways at the cellular and subcellular level, that are involved in enhancing repair and regeneration of diseased and healthy cartilage and bone.
Identification of molecules involved in the tissue responses to mechanical forces and translate these findings for the treatment of joint/bone disorders.
Development of non-invasive methods to treat joints afflicted with arthritic diseases.
Application of quantitatively optimal mechanical signals and mediators involved in mechanosignaling to repair cartilage and bone following thorough understanding of the effects of mechanical forces on the cartilage and bone.
For centuries, exercise is known to promote health. Only recently it is becoming clear that mechanical forces control a highly concerted series of biochemical events that direct many homeostatic functions of the body. This mechanoresponsiveness is especially striking in joints, where mechanical loading elicits reparative and regenerative effects. Despite this well accepted phenomenon, how exercise drives mechanoactivated joint repair is little understood. Recently, we have provided evidence that mechanical forces of physiological magnitudes are potent anti-inflammatory and reparative signals in chondrocytes and osteoblasts as well as in cartilage and bone. These signals suppress proinflammatory gene induction by inhibiting NF-?B signaling cascade via TAK1, a kinase upstream of signalosome that controls NF-?B nuclear translocation. Furthermore, mechanical signals act as potent regenerative signals and induce matrix synthesis via induction of transcription factors like Sox-9 in the cartilage and Runx-2 in the bone. We are now extending these studies to examine the signal transduction pathways that are important in tissue regeneration as well as curbing the inflammation, i.e., Wnt/beta-catenin, SMAD, and Akt signaling cascades.
On the other hand, the ongoing studies have demonstrated that exercise induces factors critical in bone remodeling. Our longterm goal is to understand their mechanisms of actions and take these basic science findings to the clinic via translational studies through collaborations with physicians, bioengineers and scientists. With the advancements of technologies for tissue repair and tissue engineering, identification of the molecules that enhance tissue's ability to self-regenerate are quite important. These molecules once delineated can then be applied in an effective manner to augment regenerative capacity of diseased and aging cartilage, as well as allow better integration of tissue engineered transplants, to repair bone afflicted with arthritic diseases.