OBJECTIVES: To investigate differentially expressed microRNAs (miRNAs) and predicted target genes over 12 days of osteoclastogenesis. METHODS: Leukophoresed buffy coats were obtained from healthy human donors (N=4) and CD14+ monocytes isolated. Osteoclastogenesis was induced by culturing cells with sRANKL and M-CSF. Freshly isolated monocytes and monocytes cultured with M-CSF alone were utilized as controls. At 4 time points, RNA was isolated and miRNA levels interrogated using microarrays (N=36.) MiRNA-mRNA target interactions for differentially expressed miRNAs were investigated using publically available algorithms. RESULTS: MiRNA profiling revealed conserved and differentially expressed miRNAs; both novel and previously reported in osteoclastogenesis. Several differentially expressed miRNAs shared predicted mRNA targets and given targets were targeted by multiple miRNAs. CONCLUSIONS: MiRNA profiling osteoclastogenesis identified previously associated miRNAs and novel miRNAs not previously described in osteoclast differentiation. In-silico analysis reveals potential mRNA targets serving as candidates for future investigation, with possible future implications in human diseases.