Figure 2.

Amino acids and peptides from hydrolyzed collagens are absorbed reaching the systemic circulation and articular cartilage, stimulating the synthesis of ECM macromolecules and chondrogenic differentiation. Native type II collagen epitopes cross the gut lumen by different mechanisms including uptake by M cells, transport across enterocytes, or through tight junctions. The epitopes are passed on to dendritic cells that once activated favor the differentiation of regulatory T cells (Tregs) at Peyer’s Patches or at mesenteric lymph nodes. Tregs exit from lymph nodes to systemic circulation through the efferent lymph and reach articular cartilage. At articular cartilage, Tregs inhibit the inflammatory cascade caused by the release of autoantigens generated as a consequence of cartilage catabolism.