The remodeling process of bone is accompanied by complex changes in the expression levels of various genes. Several approaches have been employed to detect differentially-expressed genes in regard to osteoclast differentiation. In order to identify the genes that are involved in osteoclast differentiation, we used a cDNA-array-nylon membrane. Among 1,200 genes that showed ameasurable signal, 19 genes were chosen for further study. Eleven genes were up-regulated; eight genes were down-regulated. TIS21 was one of the up-regulated genes which were highly expressed in mature osteoclasts. To verify the cDNA microarray results, we carried out RT-PCR and real-time RT-PCR for the TIS21 gene. The TIS21 mRNA level was higher in differentiated-osteoclasts when compared to undifferentiated bone-marrow macrophages. Furthermore, the treatment with $1;{mu}M$ of a TIS21 antisense oligonucleotide reduced the formation of osteoclasts from the bone-marrow-precursor cells by ~30%. These results provide evidence for the potential role of TIS21 in the differentiation of osteoclasts.