Regulation of Chondrocyte Differentiation by Changing Intercellular Distances Using Type II Collagen Microfibers

Osteoarthritis is a common degenerative disease that mainly occurs in older age groups, and the search for an effective cure remains a major global challenge. The technology of constructing 3D in vitro cartilage tissue with zonal differentiated structures for use as alternative implants for treating osteoarthritis has attracted researchers' attention. For this challenge, it is important for understanding the relationship between chondrocyte differentiation and the amount of extracellular matrix by modulating intercellular distance. This study investigates the interplay between chondrocyte differentiation and intercellular distance. Type II collagen microfibers (CMF II) were used as a distance regulator by varying their amounts. The results indicated that the secretion of cartilage-specific glycosaminoglycan after 2 weeks of differentiation from the chondrogenic cells, ATDC5, was decreased with an increased intercellular distance. Also, the shortest intercellular distance, being ATDC5 cells without CMF II, presented an upregulated gene expression profile of cartilage markers. The groups with CMF II-mediated intracellular distances, however, did not show the upregulation. The elastic modulus of the 3D samples increased depending on the amount of CMF II, relating to the differentiation preventing property of the CMF II. These findings suggest the promising potential of this approach for the modulation of chondrocyte differentiation.