Osteoclasts are the primary cells which perform bone resorption. The o
rigin of these multi-nucleated giant cells is the haematopoietic stem
cells. The differentiation pathway of the osteoclasts has so far been
well studied and the cell-lineage of these bone resorbing cells is con
sidered to be close but not identical to the monocytes/macrophages. Ow
ing to the development of in vitro culture systems for evaluating oste
oclast differentiation, it has been elucidated that various cytokines
are involved in the differentiation of the osteoclasts. However, there
is still ambiguity concerning the molecular mechanism of the differen
tiation of the osteoclasts. One approach for clarifying the molecular
mechanism is to find unique antigen molecules involved in the process
of osteoclast differentiation. In this review article, we introduce su
ch immunological studies concerning osteoclast differentiation. We als
o refer to our recent establishment of a panel of monoclonal antibodie
s recognizing rat osteoclasts. One of the monoclonal antibodies recogn
izes cell surface antigen (Kat1-antigen) expressed on cells in osteocl
ast-lineage and not on monocytes/macrophages. Cross-linking of the cel
l surface antigen using this monoclonal antibody showed that the Kat1-
antigen is the unique cell surface molecule involved in the regulation
of the affinity of the calcitonin receptor and also involved in the m
odulation of the bone resorption. In this review article, we overview,
the current issues which should be elucidated for understanding the d
ifferentiation and activation of the osteoclasts. We further emphasize
the utility of the immunological approach for solving these current t
arget issues.