|Budget Amount *help
¥2,000,000 (Direct Cost : ¥2,000,000)
Fiscal Year 1997 : ¥800,000 (Direct Cost : ¥800,000)
Fiscal Year 1996 : ¥1,200,000 (Direct Cost : ¥1,200,000)
1. Bone resorption and osteoclast differentiation through adhesion molecules on osteoblasts
In this study, we observed the following novel results : (1) mouse osteoblasts expressed ICAM-1 and the expression was increased by PTH (10ng/ml) , IL-1a (10ng/ml) or 1a, 25 (OH) _2D_3 (D_3,10^<-8>M) ; (2) in a mouse bone marrow culture system or a co-culture system of mice spleen cells and osteoblasts, TRAP-positive multinuclear cell formation by these mediators was inhibited by the addition of anti-ICAM-1 mAb and/or anti-LFA-1 mAb ; (3) In bone resorption assays, PTH,IL-1a or D_3-stimulated bone resorption was inhibited by anti-ICAM-1 mAb and/or anti-LFA-1 mAb, while the basal bone resorbing activities were not affected by these mAbs. These results indicate that cell to cell adhesion through ICAM-1/LFA-1 pathway is involved in PTH,IL-1a or D_3-induced osteoclast differentiation and bone resorption, at least in part, resulting from the induction of ICAM-1 expression on osteoblasts.
s are regulated by cellular adhesion through CD44 and hyaluronic acid pathway
The results showed that (1) chondrocytes (HCS-2/8) highly expressed CD44 ; (2) HCS-2/8 adhered to hyaluronic acid (HA) coated on plastic dish ; (3) mAb-blocking studies indicated that adhesion of HCS-2/8 to HA was mainly mediated by CD44/HA pathway ; (4) cellular adhesion to HA induced the proliferation of HCS-2/8, the expression of c-myc and TGF-b mRNA,which were reduced by CD44 mAb. Thus, HCS-2/8 effectively adhered to HA through cell surface CD44. The adhesion was also involved in cellular signals which induced cellular proliferation and expression of c-myc as well as TGF-b mRNA.
3. Expression of ICAM-1 on osteoblasts
(1) PTH and IL-1a induced-ICAM-1 expression on osteoblasts was associated with PKC pathway. (2) PTH,IL-1a or D_3 induced osteoblast differentiation, but IL-4 inhibited osteoblast differentiation and ICAM-1 expression on the cells, suggesting that the ICAM-1 expression on osteoblasts may related with the cell differentiation. Further studies are needed for evaluating the mechanism of ICAM-1 expression on osteoblasts.
4. Integrin expression on osteoblasts and cellular adhesion to extracellular matrix protein, collagen
Human osteoblasts (MG63) expressed a2b1 integrin. MG63 adhered to collagen on plastic dish. The cellular adhesion to collagen induced IL-6 mRNA expression of MG63, which was enhanced by TGF-b.