TY - JOUR
T1 - New insights on membrane mediated effects of 1α,25-dihydroxy vitamin D3 signaling in the musculoskeletal system
AU - Doroudi, Maryam
AU - Chen, Jiaxuan
AU - Boyan, Barbara D.
AU - Schwartz, Zvi
N1 - Copyright:
Copyright 2014 Elsevier B.V., All rights reserved.
PY - 2014/3
Y1 - 2014/3
N2 - 1α,25-Dihydroxy vitamin D3 [1α,25(OH)2D3] acts on cells via classical steroid hormone receptor-mediated gene transcription and by initiating rapid membrane-mediated signaling pathways. Two receptors have been implicated to play roles in 1α,25(OH) 2D3 mediated rapid signaling, the classical nuclear vitamin D receptor (VDR) and protein disulfide isomerase, family A, member 3 (Pdia3). Long term efforts to investigate the roles of these two receptors demonstrated thatPdia3 is located in caveolae, where it interacts with phospholipase A2 (PLA2) activating protein (PLAA) and caveolin-1 (Cav-1) to initiate rapid signaling via Ca++/calmodulin-dependent protein kinase II (CaMKII), PLA2, phospholipase C (PLC), protein kinase C (PKC), and ultimately the ERK1/2 family of mitogen activated protein kinases (MAPK). VDR is present on the plasma membrane, and it is required for 1α,25(OH) 2D3 induced rapid activation of Src. PDIA3+/- mice demonstrate an impaired musculoskeletal phenotype. Moreover, our studies examining mineralization of pre-osteoblasts in 3D culture have shown the physiological importance of Pdia3 and VDR interaction: knockdown of Pdia3 or VDR is characterized by impaired mineralization of the constructs.
AB - 1α,25-Dihydroxy vitamin D3 [1α,25(OH)2D3] acts on cells via classical steroid hormone receptor-mediated gene transcription and by initiating rapid membrane-mediated signaling pathways. Two receptors have been implicated to play roles in 1α,25(OH) 2D3 mediated rapid signaling, the classical nuclear vitamin D receptor (VDR) and protein disulfide isomerase, family A, member 3 (Pdia3). Long term efforts to investigate the roles of these two receptors demonstrated thatPdia3 is located in caveolae, where it interacts with phospholipase A2 (PLA2) activating protein (PLAA) and caveolin-1 (Cav-1) to initiate rapid signaling via Ca++/calmodulin-dependent protein kinase II (CaMKII), PLA2, phospholipase C (PLC), protein kinase C (PKC), and ultimately the ERK1/2 family of mitogen activated protein kinases (MAPK). VDR is present on the plasma membrane, and it is required for 1α,25(OH) 2D3 induced rapid activation of Src. PDIA3+/- mice demonstrate an impaired musculoskeletal phenotype. Moreover, our studies examining mineralization of pre-osteoblasts in 3D culture have shown the physiological importance of Pdia3 and VDR interaction: knockdown of Pdia3 or VDR is characterized by impaired mineralization of the constructs.
KW - BMP2
KW - CaMKII
KW - Mineralization
KW - Osteoblast
KW - Pdia3
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U2 - 10.1016/j.steroids.2013.10.019
DO - 10.1016/j.steroids.2013.10.019
M3 - Review article
C2 - 24291576
AN - SCOPUS:84895544922
VL - 81
SP - 81
EP - 87
JO - Steroids
JF - Steroids
SN - 0039-128X
ER -