The Necessity of the FN-Collagen I Interaction in ATDC5 Condensation

Abstract

Chondrogenic differentiation is the differentiation of stem cells into chondrocytes, which form cartilage and a foundation for bone ossification. The prerequisite step of this differentiation is known as cellular condensation, at which time cells proliferate and cellular associations increase. The extracellular matrix (ECM) drives this process and undergoes a dramatic transformation, as cells become chondrocytes. Both fibronectin (FN) and collagen I are present at condensation; however, despite the presence of fibronectin and collagen I at condensation, the impact of their interaction on this process is unknown. Using the in vitro chondrogenic model cell line, ATDC5, we have shown that both FN and collagen I are secreted and deposited into the matrix prior to condensation and remain present throughout this process. Inhibition of the FN-Collagen interaction resulted in reduced and abnormal collagen I matrix deposition. Inhibition of the FN matrix plays a role in the processing of procollagen to mature collagen. With the impact of the FN-Collagen I interaction on collagen I matrix and the dependency of collagen I on FN, inhibition of the interaction prevented condensation in the model cell line. It is the hope of this research to provide a better understanding of the chondrogenic differentiation microenvironment in order to one day improve cartilage regenerative medicine.