Transforming growth factor beta 1 (TGF‑β1), a multifunctional cytokine, induces the expression of bone remodeling gene matrix metalloproteinase‑13 (MMP‑13). CREB‑binding protein (CBP), a co‑activator and runt‑related transcription factor 2 (Runx2), a bone transcription factor, play critical roles in regulating bone‑remodeling genes. Recent advances in non‑coding RNAs have revealed the significance of microRNAs (miRNAs) and their target genes in bone physiology. The present study hypothesized that TGF‑β1 stimulated MMP‑13 expression by downregulating CBP‑targeting miRNAs and activating CBP‑mediated Runx2 acetylation in human osteoblastic cells. TGF‑β1‑downregulated miRNAs that potentially target CBP were identified. Among these miRNAs, TGF‑β1 significantly downregulated miR‑4327 in these cells. TGF‑β1 stimulated CBP, acetylated Runx2 and MMP‑13 protein expression levels in human osteoblastic cells and this effect was decreased by overexpressing miR‑4327 in these cells. In human osteoblastic cells, miR‑4327 was found to directly bind to the 3'‑untranslated region of CBP using a dual‑luciferase gene reporter assay. Thus, the present study indicated that the TGF‑β1/miR‑4327/CBP/Runx2 plays a key role in MMP‑13 expression, suggesting the clinical relevance of this axis for treating bone‑related disorders.

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