Stimulation of osteoclast formation by 1, 25-dihydroxyvitamin D requires its binding to vitamin D receptor (VDR) in osteoblastic cells: studies using VDR knockout mice

S Takeda, T Yoshizawa, Y Nagai, H Yamato… - …, 1999 - academic.oup.com
S Takeda, T Yoshizawa, Y Nagai, H Yamato, S Fukumoto, K Sekline, S Kato, T Matsumoto…
Endocrinology, 1999academic.oup.com
Previous studies have shown that 1, 25-dihydroxyvitamin D [1, 25 (OH) 2D] plays important
roles in the formation of osteoclasts through its actions on osteoblastic cells. We have
generated mice lacking vitamin D receptor (VDR) by gene targeting (VDR-/-). These mice
has tartrate-resistant acid phosphate (TRAP)-positive osteoclasts, and exhibited similar
levels of parameteres for bone resorption to those in wild type mice. The present studies
were undertaken to clarify whether effects of 1, 25 (OH) 2D on osteoclast formation require …
Abstract
Previous studies have shown that 1,25-dihydroxyvitamin D[ 1,25(OH)2D] plays important roles in the formation of osteoclasts through its actions on osteoblastic cells. We have generated mice lacking vitamin D receptor (VDR) by gene targeting (VDR-/-). These mice has tartrate-resistant acid phosphate (TRAP)-positive osteoclasts, and exhibited similar levels of parameteres for bone resorption to those in wild type mice. The present studies were undertaken to clarify whether effects of 1,25(OH)2D on osteoclast formation require VDR in osteoblasts, and to examine mechanisms of the formation of osteoclasts without VDR-mediated actions using VDF−/− mice. When wild-type calvarial osteoblasts and spleen cells were co-cultured with 1,25(OH)2D, TRAP-positive osteoclasts were formed regardless of the genotypes of spleen cells. In contrast, when osteoblasts from VDR−/− mice were co-cultured, no osteoclasts could be formed even with wild-type spleen cells. Parathyroid hormone and interleukin-1α stimulated osteoclast formation by co-cultures from VDR−/− mice, and the generated osteoclasts showed resorbing activity. These results demonstrate that VDR-mediated actions of 1,25(OH)2D in osteoblasts are essential for osteoclast formation by 1,25(OH)2D, and that functionally intact osteoclasts can be formed without 1,25(OH)2D actions under stimulations by other agents. It is suggested that osteoclastic bone resorption can be maintained without 1,25(OH)2D actions by other stimulatory agents.
Oxford University Press