The ARSB-initiated signaling regulates the CHST11 expression. ARSB silencing increased chondroitin-4-sulfation and reduced binding of galectin-3 to the more highly sulfated C4S. Wnt expression increased, due to interaction of nuclear galectin-3 with Sp1 [2]. BMP4 secretion declined, due to increased sequestration of BMP4 with more highly sulfated C4S, leading to less nuclear phospho-Smad3 and reduced CHST11 expression. The increase in C4S present when ARSB is reduced inhibited the BMP4 secretion and increased Wnt9A expression, which was mediated by galectin-3. Inverse effects of decline in ARSB on Wnt9A expression and CHST11 expression are mediated by the opposing effects of increased chondroitin 4-sulfation on binding with galectin-3 and BMP4.
[ARSB=arylsulfatase B; BMP=bone morphogenetic protein; C4S=chondroitin 4-sulfate; CHST11=carbohydrate (chondroitin 4) sulfotransferase 11; Sp=specificity protein]