Extracellular Nucleotides Selectively Induce Migration of Chondrocytes and Expression of Type II Collagen

The migration of chondrocytes from healthy to injured tissues is one of the most important challenges during cartilage repair. Additionally, maintenance of the chondrogenic phenotype remains another limitation, especially during monolayer culture in vitro. Using both the differentiated and undifferentiated chondrogenic ATDC5 cell line, we showed that extracellular nucleotides are able to increase the migration rate of chondrocytes without affecting their chondrogenic phenotype. We checked the potency of natural nucleotides (ATP, ADP, UTP, and UDP) as well as their stable phosphorothioate analogs, containing a sulfur atom in the place of one nonbridging oxygen atom in a phosphate group. We also detectedP2y1, P2y2,P2y4, P2y6,P2y12, P2y13, andP2y14mRNA transcripts for nucleotide receptors, demonstrating thatP2y1andP2y13are highly upregulated in differentiated ATDC5 cells. We showed that ADP beta S, UDP beta S, and ADP are the best stimulators of migration of differentiated chondrocytes. Additionally, ADP and ADP beta S positively affected the expression of type II collagen, a structural component of the cartilage matrix.