| Co-Investigator(Kenkyū-buntansha) |
TAKAHASHI Naoyuki Showa Univ., School of Dentistury Associate Professor, 歯学部, 助教授 (90119222)
TAKITO Jiro Showa Univ., School of Dentistry Assistant, 歯学部, 助手 (00197237)
SHINKI Toshimasa Showa Univ., School of Dentistry Lecturer, 歯学部, 講師 (90138420)
JIN Cheng He Showa Univ., School of Dentistry Assistant, 歯学部, 助手 (10205049)
ABE Etsuko Showa Univ., School of Dentistry Associate Professor, 歯学部, 助教授 (70119147)
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| Research Abstract |
We referred osteoporosis to a general disease in abnormal calcium metabolism, and approached to clarify the regulation mechanism of calcium absorption in the intestine and the functions of osteotropic factors in bone formation and resorption. Results obtained in this study could be summarized as follows :
1. By comparing chick intestinal calcium absorption between brush border and basolateral membrane fractions which were purified by saccharide gradient centrifugation, the increased calcium absorption by 1alpha, 25-dihydroxyvitamin D_3 [1alpha, 25(OH)_2D_3] was much attributive to efflux of calcium from basolateral membranes than influx of calcium from brush border membranes. Several pieces of evidence supported that calcium pump present in the basolateral membranes was Ca^<2+>, Mg^<2+>-ATPase, which contributed to the intestinal calcium transport depending upon the phosphorylation-dephosphorylation forms.
2. A 190 kDa protein was purified from conditioned media of mouse bone marrow-derived stromal cell(ST2)and primary osteoblastic cell cultures treated with 1alpha, 25(OH)_2D_3 and identified as the third component of complement(C3). The regulation of C3 by 1alpha, 25(OH)_2D_3 was under a transcriptional level, and appeared to occur tissue-specifically. The production of C3 was increased by not only 1alpha, 25(OH)_2D_3, but also local bone-resorbing agents such as IL-1, TNFalpha, and LPS. Adding 1alpha, 25(OH)_2D_3 together with antibody against C3 to bone marrow cultures greatly inhibited the formation of TPAP-positive osteoclast-like multinucleated cells.
3. Macrophages were able to differentiate into osteoclast-like cells by culturing macrophages with ST2 cells in the presence of 1alpha, 25(OH)_2D_3 and dexamethasone. When the factor(s)committing osteoclast formation was examined, it was found that M-CSF is an important factor, which commits osteoclast progenitors differentiating into mature osteoclast cells.
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