A traditional herbal decoction regulates skeletal muscle satellite cell osteogenesis and myogenesis for repairing osteosarcopenic fractures via β-catenin

Stem Cell Res Ther. 2025 Sep 26;16(1):521. doi: 10.1186/s13287-025-04642-6.

Abstract

Introduction: Osteosarcopenic fractures, an emerging geriatric syndrome characterized by sarcopenia-osteoporotic fractures coexistence, delayed fracture healing, and elevated risk of re-fracture. Limited research has investigated the mechanisms by which skeletal muscle satellite cells (SMSCs) promote muscle regeneration and osteoporotic fracture healing. The aim of this study was to investigate the impact of a traditional herbal decoction (HD), the Invigorate the Spleen and Tonify the Kidney Formula, on SMSC regulation, muscle regeneration, and fracture healing.

Method: Using conditional knockout mice, the role of SMSCs in promoting fracture healing and mitigating sarcopenia was evaluated by visualizing the fracture area and surrounding muscle tissue. The signaling pathways involved were comprehensively analyzed using a combination of Western blotting, real-time PCR analysis, immunohistochemical staining, and immunofluorescent staining. And the key elements and compounds facilitating osteogenesis and myogenesis were identified using HPLC and network pharmacology analysis.

Results: This study demonstrated that the herbal decoction mediates the β-catenin signaling pathway, mobilizes SMSCs to migrate to the fracture area, facilitates their osteogenic and myogenic differentiation, and enhances osteoporotic fracture healing. Knockdown of β-catenin in SMSCs in Pax7-CreERT2/+;β-cateninfx/fx conditional knockout mice led to sarcopenia and osteoporosis. Additionally, the herbal decoction significantly increased bone mass, repaired bone microstructure, and promoted muscle fiber remodeling around fractures in mice.

Conclusions: These findings provide the first evidence that the HD, as a β-catenin agonist, not only promotes fracture healing by modulating the osteogenic and myogenic effects of SMSCs but also ameliorates sarcopenia. This study offers practical evidence supporting the formula as a promising therapeutic candidate for treating osteosarcopenic fractures.

Keywords: Herbal decoction; Osteoporotic fracture; Osteosarcopenia; Skeletal muscle stem cells; β-catenin.

MeSH terms

  • Animals
  • Cell Differentiation / drug effects
  • Drugs, Chinese Herbal* / pharmacology
  • Fracture Healing* / drug effects
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Muscle Development* / drug effects
  • Osteogenesis* / drug effects
  • Osteoporotic Fractures* / drug therapy
  • Osteoporotic Fractures* / metabolism
  • Osteoporotic Fractures* / pathology
  • Sarcopenia* / drug therapy
  • Sarcopenia* / metabolism
  • Satellite Cells, Skeletal Muscle* / cytology
  • Satellite Cells, Skeletal Muscle* / drug effects
  • Satellite Cells, Skeletal Muscle* / metabolism
  • beta Catenin* / genetics
  • beta Catenin* / metabolism

Substances

  • beta Catenin
  • Drugs, Chinese Herbal