Cartilage differentiation and the actin cytoskeleton

Chondrogenesis, e.g., the formation of cartilage from precursor cells, is characterized by drastic changes in cell shape and size. This involves major reorganization of the cytoskeleton, in particular the actin network. However, we have known for several decades that the actin cytoskeleton does not merely and passively respond to upstream signals but instead actively controls chondrocyte cell fate and gene expression. Recent years have provided new insights into the regulation of actin organization both during chondrogenesis (in particular through signaling proteins of the Rho GTPase family) and into the downstream mechanisms connecting actin dynamics to chondrocyte gene expression (e.g., through the chondrocyte master transcription factor Sox9). These insights increase our understanding of the fundamental processes controlling skeletal development and are also highly relevant to disturbances of normal chondrocyte function in diseases such as chondrodysplasias and osteoarthritis

The minor collagens in articular cartilage

ABSTRACT Articular cartilage is a connective tissue consisting of a specialized extracellular matrix (ECM) that dominates the bulk of its wet and dry weight. Type II collagen and aggrecan are the main ECM proteins in cartilage. However, little attention has been paid to less abundant molecular components, especially minor collagens, including type IV, VI, IX, X, XI, XII, XIII, and XIV, etc. Although accounting for only a small fraction of the mature matrix, these minor collagens not only play essential structural roles in the mechanical properties, organization, and shape of articular cartilage, but also fulfil specific biological functions. Genetic studies of these minor collagens have revealed that they are associated with multiple connective tissue diseases, especially degenerative joint disease. The progressive destruction of cartilage involves the degradation of matrix constituents including these minor collagens. The generation and release of fragmented molecules could generate novel biochemical markers with the capacity to monitor disease progression, facilitate drug development and add to the existing toolbox for in vitro studies, preclinical research and clinical trials