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The Runx2 switch: unlocking osteoblast-related disorders through signaling pathways and non-coding RNAs

Somayeh Aslani1, Ashkan Kalantary-Charvadeh1, Roghayeh Abbasalipourkabir1

  • 1Department of Clinical Biochemistry, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran.

Experimental Cell Research
|February 1, 2026
PubMed

Insights

Runt-related transcription factor 2 (Runx2) is crucial for bone formation. This review explores how signaling pathways and non-coding RNAs regulate Runx2, offering insights into treating bone disorders.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Background:

  • Osteoblasts, derived from mesenchymal stem cells (MSCs), are vital for bone formation.
  • Dysregulation of osteoblast differentiation contributes to bone-related disorders.
  • Runt-related transcription factor 2 (Runx2) is a master regulator of osteoblast differentiation.

Purpose of the Study:

  • To review the regulatory mechanisms governing Runx2 expression and function during osteoblast differentiation.
  • To explore the interplay between signaling pathways, non-coding RNAs, and Runx2 in osteogenesis.
  • To highlight the therapeutic potential of targeting these regulatory networks for bone disorders.

Main Methods:

  • Literature review focusing on molecular mechanisms of osteoblast differentiation.
  • Analysis of signaling pathways, transcription factors, and non-coding RNA networks.
  • Integration of data on competing endogenous RNA (ceRNA) interactions involving Runx2.

Main Results:

  • Runx2 expression and activity are tightly controlled by signaling pathways and a complex post-transcriptional ceRNA network.
  • Long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) act as sponges for microRNAs (miRNAs), modulating Runx2 levels.
  • Signaling pathways influence Runx2 indirectly by regulating osteo-regulatory miRNAs.

Conclusions:

  • Runx2 is a central node in osteoblast differentiation, regulated by intricate molecular interactions.
  • Understanding the ceRNA network and signaling pathways offers novel therapeutic strategies for bone diseases.
  • Targeting Runx2-associated regulatory elements holds promise for regenerative medicine in bone repair.
Keywords:
Bone developmentCircular RNALong non-coding RNAMesenchymal stem cellsRunx2microRNAs

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