Ten‐m/Odz3 regulates migration and differentiation of chondrogenic ATDC5 cells via RhoA‐mediated actin reorganization

Abstract Tenascin‐like molecule major (Ten‐m)/odd Oz (Odz), a type II transmembrane molecule, is well known to modulate neural development. We have reported that Ten‐m/Odz3 is expressed in cartilaginous tissues and cells. Actin cytoskeleton and its regulator ras homolog gene family member A (RhoA) are closely associated with chondrogenesis. The present study aimed to evaluate the function and molecular mechanism of Ten‐m/Odz3 during chondrogenesis, focusing on RhoA and the actin cytoskeleton. Ten‐m/Odz3 was expressed in precartilaginous condensing mesenchyme in mouse limb buds. Ten‐m/Odz3 knockdown in ATDC5 induced actin cytoskeleton reorganization and change of cell shape through modulation of RhoA activity and FGF2 expression. Ten‐m/Odz3 knockdown suppressed ATDC5 migration and expression of genes associated with chondrogenesis, such as Sox9 and type II collagen, via RhoA. On the other hand, Ten‐m/Odz3 knockdown inhibited proliferation of ATDC5 in a RhoA‐independent manner. These findings suggest that Ten‐m/Odz3 plays an important role in early chondrogenesis regulating RhoA‐mediated actin reorganization.