Arthritis is a widespread debilitating disease in which joint cartilage gets degraded. Due to limited regeneration ability, cartilage tissues are often permanently lost. Understanding the mechanisms of cartilage formation and degradation is essential to devising strategies to regenerate cartilage and treat arthritis. Our research focuses on two areas:

1. Mechanism of cartilage development.
The initial formation of cartilage tissue takes place in the embryo. One of our model systems for studying cartilage formation is the somite, which gives rise to multiple cell fates including dermis, muscle and cartilage of the vertebrae and ribs. Recently, we found that a Sonic hedgehog (Shh) concentration gradient elicits patterns of different cell fates within the somites in a morphogen-like manner, with higher levels of Shh promoting the cartilage cell fate, and lower levels of Shh promoting the muscle cell fate (Cairns et al., Developmental Biology 2008). Interaction of factors within the somite further demarcates the fields of muscle and cartilage. After cartilage cell fate is specified, the developing cartilage continues to be influenced by signals secreted from the surrounding tissues such as muscle or synovium. To study the mechanisms that lead to the determination of cartilage cell fate and the development of cartilage tissue, we use both chicken and mouse models and a combined approach of embryology (e.g. tissue isolation, in vivo gene delivery and in situ hybridization) and molecular biology.

Fig.1. Cartilage-specific factor Nkx3.2 inhibits muscle cell fate. A. Virally expressing Nkx3.2 (green) inhibits the expression of Pax3, a muscle marker (red). B. Electroporation of Nkx3.2 (green) into muscle progenitors resulted in disruption of muscle marker Myosin (red) (arrows).

Fig.2. Schematic diagram of cartilage regulation.

2. Cartilage regeneration.
We are developing novel strategies to integrate concepts and approaches from developmental biology studies with tissue engineering, in order to achieve our ultimate goal of engineering stronger and more stable cartilage tissue. Cartilage tissue engineering involves reconstructing three-dimensional (3D) tissues by seeding cartilage cells in natural or synthetic scaffolds. Despite the use of a variety of cell types and scaffolds to engineer cartilage that mimics native cartilage, regenerated cartilage is still not satisfactory, especially in terms of biomechanics, stability and host integration. Our laboratory recently discovered that muscle cell-expressing factors have the capacity of promoting matrix production in engineered cartilage of three-dimensional cultures (Cairns et al, J. Ortho. Res. 2009). Currently we are investigating the nature of such pro-cartilage signals, as well as the impact of scaffold material on the stability of engineered cartilage. These studies are done through the collaboration with Dr. David Kaplan from the Biomedical Engineering Department at Tufts University, and with Dr. Elizabeth Matzkin from the Orthopaedics Department of Tufts Medical Center.

Fig.3. Muscle and cartilage cells in three-dimensional collagen scaffolds. Red staining indicates the expression of cartilage marker collagen II in cartilage cells. Green staining indicates the expression of muscle marker desmin in muscle cells.