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LDL receptor affects the skeletal muscle and bone microstructure of female mouse through the Wnt/β-catenin signaling

Yue Hu1, Huiling Liu1,2, Chaoyue Zhao1

  • 1School of Basic Medical Sciences, Youjiang Medical University for Nationalities, Baise, 533000, Guangxi, China.

Journal of Molecular Histology
|February 18, 2026
PubMed
Abstract

Insights

Targeting LDLR knockdown in skeletal muscle can reverse age-related muscle loss and bone density decline by activating the Wnt/β-catenin pathway, offering a new therapeutic strategy for osteosarcopenia.

Area of Science:

  • Biomedical Science
  • Aging Research
  • Musculoskeletal Biology

Background:

  • Osteosarcopenia, a dual condition of age-related sarcopenia and osteoporosis, lacks effective treatments.
  • Aging leads to significant decline in muscle mass, strength, and bone integrity.

Purpose of the Study:

  • To investigate if skeletal muscle-specific LDLR knockdown can reverse functional decline in osteosarcopenia.
  • To explore the role of the Wnt/β-catenin signaling pathway in this process.

Main Methods:

  • Elderly mice underwent LDLR knockdown in skeletal muscle.
  • Assessed grip strength, muscle histology, bone microarchitecture via micro-CT, and Wnt pathway components.
  • Utilized RT-qPCR and Western blot for pathway analysis.

Main Results:

  • LDLR knockdown significantly improved grip strength and upregulated key muscle proteins (MYF5, MYH2).
  • Enhanced trabecular bone parameters, including bone volume and thickness.
  • Activated the β-catenin signaling pathway, indicating therapeutic potential.

Conclusions:

  • Skeletal muscle LDLR knockdown is a promising strategy to combat sarcopenia.
  • Reactivation of the Wnt/β-catenin pathway is crucial for these improvements.
  • This approach offers a potential therapeutic target for musculoskeletal aging.
Keywords:
Bone densityLDLSarcopeniaSkeletal muscle

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