A review of 1α,25(OH)2D3 dependent Pdia3 receptor complex components in Wnt5a non-canonical pathway signaling

Wnt5a and 1 alpha,25-dihydroxyvitamin D3 [1 alpha,25(OH)(2)D-3] regulate endochondral ossification. 1a,25 (OH)(2)D-3 initiates its calcium-dependent effects via its membrane-associated receptor, protein disulfide isomerase A3 (Pdia3). 1 alpha,25(OH)(2)D-3 binding to Pdia3 triggers the interaction between Pdia3 and phospholipase A(2) (PLA(2))-activating protein (PLAA), resulting in downstream activation of calcium/calmodulin-dependent protein kinase II (CaMKII), PLA(2), and protein ldnase C (PKC). Wnt5a initiates its calcium-dependent effects via binding its receptors Frizzled2 (FZD2) and Frizzled5 (FZD5) and receptor tyrosine kinase-like orphan receptor 2 (ROR2), activating intracellular calcium release and stimulating PKC and CaMKII. Recent efforts to determine the inter-relation between Wnt5a and 1 alpha,25(OH)(2)D-3 signaling pathways have demonstrated that Wnt5a signals through a CaMKII/PLA(2)/PGE(2)/PKC cascade in chondrocytes and osteoblasts in which the components of the Pdia3 receptor complex were required. Furthermore, ROR2, but not FZD2 or FZD5, was required to mediate the calcium-dependent actions of 1 alpha,25(OH)(2)D-3. This review provides evidence that 1 alpha,25(OH)(2)D-3 and Wnt5a mediate their calcium-dependent pathways via similar receptor components and proposes that these pathways may interact since they are competing for the same receptor complex components. (C) 2015 Elsevier Ltd. All rights reserved.