Transcriptional regulation of the production of the third component of complement (C3) by 1 alpha,25-dihydroxyvitamin D3 in mouse marrow-derived stromal cells (ST2) and primary osteoblastic cells.
We have purified a 190-kDa protein produced by mouse marrow-derived stromal cells (ST2) in response to 1 alpha,25-dihydroxyvitamin D3 [1 alpha,25-(OH)2D3] and unequivocally identified it as mouse complement C3 (C3). In this study we examined the regulation by 1 alpha,25-(OH)2D3 of C3 production in ST2 cells at both the transcriptional and translational levels. 1 alpha,25-(OH)2D3 greatly increased the protein production of C3 at 24 h, and it attained a maximum at 72 h. C3 mRNA stimulation by 1 alpha,25-(OH)2D3 was initiated at 12 h and reached a maximum at 48 h. 1 alpha,25-(OH)2D3 increased the expression of C3 mRNA dose-dependently, ranging from 10(-10)-10(-8) M. The increase in the C3 production in response to 1 alpha,25-(OH)2D3 appeared to occur at a transcriptional level, since actinomycin-D completely inhibited both mRNA expression and protein production of C3 induced by 1 alpha,25-(OH)2D3. Besides 1 alpha,25-(OH)2D3, local bone-resorbing agents, such as interleukin-1 alpha, tumor necrosis factor-alpha, and lipopolysaccharides, also stimulated the expression of C3 mRNA, not only in ST2 cells, but also in primary osteoblastic cells. C3 production by hepatocytes occurred regardless of the presence or absence of 1 alpha,25-(OH)2D3. These results clearly indicate that 1 alpha,25-(OH)2D3 tissue-specifically regulates the synthesis of C3 in bone. Bone C3 may play an important role in bone metabolism.
Department of Biochemistry, Showa University School of Dentistry, Tokyo, Japan.
M H
MH
Hong
C H
CH
Jin
T
T
Sato
Y
Y
Ishimi
E
E
Abe
T
T
Suda
D000818:Animals; D001853:Bone Marrow / Q000378:metabolism*; D001854:Bone Marrow Cells; D002117:Calcitriol / Q000494:pharmacology*; D003176:Complement C3 / Q000096:biosynthesis* / Q000235:genetics; D008099:Liver / Q000166:cytology / Q000378:metabolism; D008297:Male; D051379:Mice; D010006:Osteoblasts / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects
D003176:Complement C3; D012333:RNA, Messenger; D002117:Calcitriol