Open Access

MicroRNA‑4327 regulates TGF‑β1 stimulation of matrix metalloproteinase‑13 expression via CREB‑binding protein‑mediated Runx2 acetylation in human osteoblasts

  • Authors:
    • Rushil Kolipaka
    • Induja Magesh
    • S. Karthik
    • M. R. Ashok Bharathy
    • I. Saranya
    • D. Preetha
    • N. Selvamurugan
  • View Affiliations

  • Published online on: November 19, 2024     https://doi.org/10.3892/etm.2024.12770
  • Article Number: 20
  • Copyright: © Kolipaka et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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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January-2025
Volume 29 Issue 1

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Spandidos Publications style
Kolipaka R, Magesh I, Karthik S, Ashok Bharathy M, Saranya I, Preetha D and Selvamurugan N: MicroRNA‑4327 regulates TGF‑β1 stimulation of matrix metalloproteinase‑13 expression via CREB‑binding protein‑mediated Runx2 acetylation in human osteoblasts. Exp Ther Med 29: 20, 2025.
APA
Kolipaka, R., Magesh, I., Karthik, S., Ashok Bharathy, M., Saranya, I., Preetha, D., & Selvamurugan, N. (2025). MicroRNA‑4327 regulates TGF‑β1 stimulation of matrix metalloproteinase‑13 expression via CREB‑binding protein‑mediated Runx2 acetylation in human osteoblasts. Experimental and Therapeutic Medicine, 29, 20. https://doi.org/10.3892/etm.2024.12770
MLA
Kolipaka, R., Magesh, I., Karthik, S., Ashok Bharathy, M., Saranya, I., Preetha, D., Selvamurugan, N."MicroRNA‑4327 regulates TGF‑β1 stimulation of matrix metalloproteinase‑13 expression via CREB‑binding protein‑mediated Runx2 acetylation in human osteoblasts". Experimental and Therapeutic Medicine 29.1 (2025): 20.
Chicago
Kolipaka, R., Magesh, I., Karthik, S., Ashok Bharathy, M., Saranya, I., Preetha, D., Selvamurugan, N."MicroRNA‑4327 regulates TGF‑β1 stimulation of matrix metalloproteinase‑13 expression via CREB‑binding protein‑mediated Runx2 acetylation in human osteoblasts". Experimental and Therapeutic Medicine 29, no. 1 (2025): 20. https://doi.org/10.3892/etm.2024.12770