|Budget Amount *help
¥2,800,000 (Direct Cost : ¥2,800,000)
Fiscal Year 1999 : ¥900,000 (Direct Cost : ¥900,000)
Fiscal Year 1998 : ¥1,900,000 (Direct Cost : ¥1,900,000)
1. The expression of adhesion molecules on osteoblast by bone resorbing factors.
The expression of intracellular adhesion molecule-1 (ICAM-1). The expression of ICAM-1 on rat osteoblast increased 24 h after the addition of parathyroid hormone PTH) and interleukin-1α (IL-1α), and 48-98 h after, that of 1, 25, (OH)ィイD22ィエD2DィイD23ィエD2(DィイD23ィエD2). However, prostaglandin EィイD22ィエD2 (PGEィイD22ィエD2) did not modulate the expression on the osteoblast.
2. Bone resorbing factor-induced osteoclast formation and bone resorption that are associated with cellular adhesion through adhesion molecules.
1) PTH, IL-1α and DィイD23ィエD2-induced TRAP positive multinuclear cell formation in coculture of mouse bone marrow cells and osteoblasts was inhibited dose-dependently by the addition of ICAM-1 and/or LFA-1 antibody. The same result was observed in coculture of mouse spleen cells and osteoblasts. 2) ィイD145ィエD1Ca release from cultured newborn mouse calvarae induced by PHT, IL-1α DィイD23ィエD2, was also inhibited b
y the addition of ICAM-1 and/or LFA-1 antibody. 3) These antibodies inhibited PTH, IL-1α and DィイD23ィエD2-induced pit formation in unfractionated bone cells cultured on dentine slice. 4) The expression of oteoclast differentiation factor (ODF/RANKL) and osteoclastgenesis inhibitory factor (OCIF) mRNA on osteoblast cultured with or without PTH and IL-1α was not modulated by the addition of ICAM-1 and/or LFA-1 antibody.
Summary : Cell-to-cell interaction is required for the differentiation of osteoclast progenotor as well as osteoclast function. Our study indicated that cellular adhesion of osteoblast to osteoclast progenitor through ICAL-1/LFA-1 binding is involved in osteoclast formation and osteoclast activity. Recent studies indicated that binding of ODF on osteoblast and RANK on osteoclast progenitor is involved in osteoclast differentiation. Since PTH and IL-1α-stimulated ODF and OCIF mRNA expression on osteoblast was not modulated by the addition of ICAM-1 and/or LFA-1 antibody, it is suggested that cellular adhesion of osteoblast and osteoclast progenitor by ICAL-1/LFA-1 support theinteraction of ODA/RANK involved in osteoclast formation. We propose that osteoclast differentiation and bone resorption stimulated by PTH, IL-1α and DィイD23ィエD2 may be facilitated by induction of ICAM-1 expression on mouse osteoblast and ICAM-1-mediated cell-to cell adhesion of osteoblast and osteoclast precussor.