Leukemia inhibitory factor/differentiation-stimulating factor (LIF/D-factor): Regulation of its production and possible roles in bone metabolism

✍ Scribed by Yoshiko Ishimi; Etsuko Abe; Cheng He Jin; Chisato Miyaura; Mei Hua Hong; Midori Oshida; Hisashi Kurosawa; Yuri Yamaguchi; Mikio Tomida; Motoo Hozumi; Tatsuo Suda

• Publisher: John Wiley and Sons
• Year: 1992
• Tongue: English
• Weight: 849 KB
• Volume: 152
• Category: Article
• ISSN: 0021-9541
• DOI: 10.1002/jcp.1041520110

✦ Synopsis

Leukemia inhibitory factoridilferenti at ion-sti mu 1 ati ng factor (LI F/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, TNFcr, and LPS strongly induced expression of LIFiD-factor mRNA in both clonal MC3T3-El cells and primary osteoblast-like cells. Neither parathyroid hormone nor la,25-dihydroxyvitamin D, stimulated cxpression of LIF/D-factor mRNA.

LIFiD-factor per se did not stimulate expression of its own mRNA.

Appreciable amounts of 1 IFiD-factor were detected in synovial fluids from rheumatoid arthritis (KA) patients but not in those with osteoarthritis (OA). Simultaneous treatment with LIFiD-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 boneresorbing cytokines such as IL-l and IL-6 involved in the bone resorption seen in the joints of RA patienls.

LIFiD-factor specifically bound to MC3T3-El cells with an apparcnt dissociation constant of 161 p M and 1,100 binding sitesicell. LIFiD-factor dose-dependently suppressed incorporation of ['Hlthymidine into MC3T3-EI 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 i n conjugation with other osteotropic factors.