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O-GlcNAcylation: A bridge for regulating the function of the "heart-kidney-bone axis"

Shuangcui Wang1, Maojuan Guo2, Bo Yang3

  • 1Department of Orthopedic Surgery, Hebei Medical University Third Hospital, Shijiazhuang, Hebei, China.

Biochemistry and Biophysics Reports
|May 27, 2026
PubMed

Insights

O-linked N-acetylglucosamine (O-GlcNAc) glycosylation is a key regulator of the heart-kidney-bone axis. Understanding O-GlcNAcylation

Area of Science:

  • Biochemistry
  • Physiology
  • Pathology

Background:

  • The heart, kidney, and bone systems are interconnected, forming the "heart-kidney-bone axis."
  • Cardiorenal syndrome, renal bone disease, and cardiovascular calcification in CKD-MBD exemplify axis dysfunction.
  • The underlying molecular mechanisms regulating this axis remain incompletely understood.

Purpose of the Study:

  • To systematically review the role of O-linked N-acetylglucosamine (O-GlcNAc) glycosylation in the heart, kidney, and skeletal systems.
  • To explore the cross-organ regulatory mechanisms of O-GlcNAcylation within the "heart-kidney-bone axis."
  • To provide novel insights for mechanism analysis and targeted therapies for related comorbidities.

Main Methods:

  • Literature review focusing on O-GlcNAcylation.
  • Analysis of O-GlcNAc's role in cardiovascular, renal, and bone physiology and pathology.
  • Examination of the hexosamine biosynthesis pathway (HBP) and its integration of nutritional and stress signals.

Main Results:

  • O-GlcNAcylation is a dynamic post-translational modification integrating cellular signals.
  • This modification is extensively involved in regulating cellular functions crucial to heart, kidney, and bone health.
  • O-GlcNAcylation plays a significant role in the progression of diseases affecting these organs.

Conclusions:

  • O-GlcNAcylation is a critical molecular player in the "heart-kidney-bone axis."
  • Understanding its regulatory network offers new avenues for therapeutic interventions.
  • Targeting O-GlcNAcylation may provide novel strategies for managing complex comorbidities.

Keywords:
BonesHeartHeart-kidney-bone axisInter-organ communicationKidneyO-GlcNAcylation

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