Autologous chondrocyte implantation (ACI) is a state-of-the-art, FDA approved procedure to treat articular cartilage defects. In this procedure small pieces of cartilage (two tic-tacs in size) are harvested from a non-diseased region of a patient’s joint. The cartilage is digested to liberate cartilage cells, or chondrocytes, within the tissue. Chondrocytes are then expanded for cell number by in vitro monolayer passaging. The passaged cells are implanted into damaged cartilage regions to stimulate repair tissue formation. Unfortunately, passaged cells are dedifferentiated. The repair tissue formed by dedifferentiated cells ultimately fails due to the formation of fibrocartilage, which is biomechanically inferior to articular cartilage.

Implicit in chondrocyte dedifferentiation is the reorganization of F-actin from a cortical organization into stress fibers. While treatment of passaged chondrocytes with anti-actin agents (cytochalasins/latrunculins) abolishes stress fibers and represses fibrocartilage formation, these anti-actin treatments are not specific. Not only do they depolymerize actin stress fibers, but they also prevent the formation of cortical actin which is essential for chondrocyte function (i.e. matrix export). In our lab, we are developing new methodologies to abolishes actin stress fibers while maintaining cortical actin in passaged cells. This will lead to the redifferentiation of passaged chondrocytes that have the potential to successfully repair cartilage damage.

Actin signaling may play a role in Osteoarthritis. Studies show that treatment of chondrocytes with Osteoarthritis inducing cytokines (i.e. interleukin-1, interleukin-6, tumor necrosis factor-α) activates actin polymerization leading to the production of matrix degradative enzymes, such as matrix metalloproteases. However, a major limitation is that previous studies used in vitro isolated chondrocytes cultured in two-dimensions on culture vessels. It is widely accepted that actin organization is context (culture) dependent. To date, there is a very little evidence to show that actin reorganization occurs within the native cartilage environment. Using new imaging high-to-super resolution imaging protocols that we have developed, we are examining actin reorganization in greater-than-before detail, in real time, and in the authentic three-dimensional cartilage tissue architecture. Our projects aim to address the question of how does actin reorganization actively regulate Osteoarthritis?

The ocular lens is a transparent tissue situated in the front of the eye that functions to fine focus light onto the retina. The lens must be clear for proper function. However, with age or injury, lens transparency can be lost resulting in cataracts, which are defined as any opacity in the lens that results in cloudy vision. Cataracts is the most common cause of vision loss after the age of forty and the leading cause of blindness world-wide.

A cause of cataracts is transdifferentiation of the lens epithelial cells (at the anterior region of the lens) into myofibroblasts through the process of epithelial-mesenchymal transition. Early stages of epithelial-mesenchymal transition involve reorganization of cortical actin into stress fibers. While preventing stress fiber formation has been identified as a potential opportunity to prevent epithelial-mesenchymal transition, strategies that specifically target actin stress fiber populations without affecting cortical (epithelial cell) F-actin networks remain elusive. We aim to address the question of what regulates stress fiber formation in lens epithelial cells? And, can we target actin stress fiber formation to prevent cataract formation?