The role of LFA-1 in osteoclast development induced by co-cultures of mouse bone marrow cells and MC3T3-G2/PA6 cells.
Interactions between leukocyte function-associated antigen-1 (LFA-1) and intercellular adhesion molecule-1 (ICAM-1) influence the development of osteoclasts. However, little is known about how these adhesion molecules are involved in the process of osteoclast development. This study evaluated the role of LFA-1 and its ligands in osteoclast development and bone resorption. Co-cultures of bone marrow cells from LFA-1-deficient mice and MC3T3-G2/PA6 (PA6) cells were cultured in the presence of 1alpha,25(OH)2D3 and dexamethasone for 7 days. The number of TRAP-positive cells that were generated by bone marrow cells from LFA-1-deficient mice was smaller than that generated by bone marrow cells from wild-type mice. In addition, the bone-resorbing activity of osteoclast-like cells that were generated from LFA-1-deficient mice was lower than that generated by osteoclast-like cells from wild-type mice. Immunofluorescence flow cytometry showed that osteoclast stromal PA6 cells expressed the cell adhesion molecules, ICAM-1 and VCAM-1. When monoclonal antibodies to mice VCAM-1, CD11b or CD18 were added separately to the co-culture system, the number of TRAP-positive cells that were generated from LFA-1-deficient mice was 20-30% smaller than that generated from wild-type mice. The formation of TRAP-positive cells from both LFA-1 deficient and wild-type mice was especially inhibited by anti-CD18 antibody, in comparison to the addition of normal IgG serum. These results suggest that LFA-1 adhesion molecules play a role in osteoclast development by affecting adhesion between stromal cells and osteoclast progenitors before the occurrence of ODF-ODF receptor signaling. CD18 appears to be a key adhesion molecule in cell-to-cell contacts during the early stage of osteoclast development.
Department of Operative Dentistry, Kanagawa Dental College, Yokosuka, Japan. nobu0337@kdcnet.ac.jp
N
N
Tani-Ishii
J M
JM
Penninger
G
G
Matsumoto
T
T
Teranaka
T
T
Umemoto
D016475:3T3 Cells; D000818:Animals; D001854:Bone Marrow Cells; D001862:Bone Resorption / Q000503:physiopathology; D018821:CD18 Antigens / Q000502:physiology*; D002448:Cell Adhesion / Q000502:physiology; D002460:Cell Line; D002469:Cell Separation; D018920:Coculture Techniques; D003804:Dentin / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D018799:Intercellular Adhesion Molecule-1 / Q000502:physiology*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010006:Osteoblasts / Q000502:physiology; D010010:Osteoclasts / Q000502:physiology*; D013234:Stem Cells / Q000502:physiology
D018821:CD18 Antigens; D016169:Lymphocyte Function-Associated Antigen-1; D018799:Intercellular Adhesion Molecule-1