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MicroRNAs play important roles during cell reprogramming and differentiation. In this study, we identified the miR‐497∼195 cluster, a member of the miR‐15 family, as strongly upregulated with age of postnatal bone development in vivo and late differentiation stages of primary osteoblasts cultured in vitro. Early expression of miR‐195–5p inhibits differentiation and mineralization. Microarray analyses along with quantitative PCR demonstrate that miR‐195–5p alters the gene regulatory network of osteoblast differentiation and impairs the induction of bone morphogenetic protein (BMP) responsive genes. Applying reporter gene and Western blot assays, we show that miR‐195–5p interferes with the BMP/Smad‐pathway in a dose‐dependent manner. Systematically comparing the changes in mRNA levels in response to miR‐195–5p overexpression with the changes observed in the natural course …