Bone resorption mechanisms on LPS in human osteoclast-like cells formation system

1992 Fiscal Year Final Research Report Summary

• Project/Area Number: 03670900
• Research Category: Grant-in-Aid for General Scientific Research (C)
• Allocation Type: Single-year Grants
• Research Field: Conservative dentistry
• Research Institution: Meikai University School of Dentistry
• Principal Investigator: KURIHARA Noriyoshi Meikai University Dentistry Lecturer, 歯学部, 講師 (10186512)
• Project Period (FY): 1991 – 1992
• Keywords: LPS / Osteoclast / Osteoclast-precursor

Research Abstract

Lipopolysaccharides(LPS) has very important roles in occuring periodontal disease and bone resorption of alveoral bone. However, no studies have been reported in which LPS induce osteoclasts formation in human cells. Recently we have shown that long term human umbilical cord blood cultures can be adapted to form multinucleated cell(MNC) that express an osteoclast phenotype (multinucleated, presence of tartrate resistant acid phosphatase activity, contraction in response to calcitonin, calcitonin receptor, formation of resorption lacunae on calcified matrices and cross-reactivity with the mAb 23C6(CD-51), which preferentially binds osteoclasts in bone biopsy specimens). This culture suggested that the CFU-GM (the granulocyte-macrophage progentor cells) is the pro-genitor cell for osteoclast. In this experiment, we studied the effect of LPS on osteoclasts formation. Addition of LPS (10-100ng/ml) to these cultures significantly increase MNC formation, with 50% of the MNC expressing an antigen which cross-reacts with the mAb 23C6. Addition of anti-human IL-1 to cultures treated with LPS totally inhibited the increase in MNC formation stimulated by LPS. Further, conditiond madia from these cultures exposed to LPS contained elevated levels of IL-1alphaand beta (47pg/ml of IL-1alpha and 31pg/ml of IL-1beta compared to under 5pg/ml in control cultures 12h. after LPS addition). These results strongly suggested that LPS significantly stimulated MNC formation in human cord blood cultures, and preferentially stimulated formation of MNC expressing the antigen recognized by 23C6 mAb. We further indicate that the effects of LPS in this system appear to be mediated by induction ofIL-1, a potent stimulator of osteoclasts formation.