LEUKEMIA INHIBITORY FACTOR DIFFERENTIATION-STIMULATING FACTOR (LIF/D-FACTOR) - REGULATION OF ITS PRODUCTION AND POSSIBLE ROLES IN BONE METABOLISM

被引:63
作者
ISHIMI, Y
ABE, E
JIN, CH
MIYAURA, C
HONG, MH
OSHIDA, M
KUROSAWA, H
YAMAGUCHI, Y
TOMIDA, M
HOZUMI, M
SUDA, T
机构
[1] SHOWA UNIV, SCH DENT, DEPT BIOCHEM, TOKYO 142, JAPAN
[2] TOKYO TEISHIN HOSP, DEPT ORTHOPED, TOKYO 102, JAPAN
[3] SAITAMA CANC CTR, RES INST, DEPT CHEMOTHERAPY, SAITAMA 362, JAPAN
关键词
D O I
10.1002/jcp.1041520110
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Leukemia inhibitory factor/differentiation-stimulating factor(LIF/D-factor), expression of its mRNA, and possible roles in bone metabolism were studied in murine primary and clonal osteoblast-like cells. Local bone-resorbing factors such as IL-1, TNF-alpha, and LPS strongly induced expression of LIF/D-factor mRNA in both clonal MC3T3-E1 cells and primary osteoblast-like cells. Neither parathyroid hormone nor 1-alpha,25-dihydroxyvitamin D3 stimulated expression of LIF/D-factor mRNA. LIF/D-factor per se did not stimulate expression of its own mRNA. Appreciable amounts of LIF/D-factor were detected in synovial fluids from rheumatoid arthritis (RA) patients but not in those with osteoarthritis (OA). Simultaneous treatment with LIF/D-factor, IL-1, and IL-6 at the concentrations found in synovial fluids from RA patients greatly enhanced bone resorption, though these cytokines did not stimulate bone resorption when separately applied. This suggests that LIF/D-factor produced by osteoblasts is in concert with other bone-resorbing cytokines such as IL-1 and IL-6 involved in the bone resorption seen in the joints of RA patients. LIF/D-factor specifically bound to MC3T3-E1 cells with an apparent dissociation constant of 161 pM and 1,100 binding sites/cell. LIF/D-factor dose-dependently suppressed incorporation of [H-3]thymidine into MC3T3-E1 cells. In addition, it potentiated the alkaline phosphatase activity induced by retinoic acid, though LIF/D-factor alone had no effect on enzyme activity. These results suggest that LIF/D-factor is involved in not only osteoclastic bone resorption but also osteoblast differentiation in conjugation with other osteotropic factors.
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页码:71 / 78
页数:8
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