Synergistic effects of herbal compounds to promote osteoporotic fracture repair through upregulation of β-catenin signaling in skeletal muscle satellite cells

Abstract

Background and purpose: Osteoporotic fracture (OPF) disrupts the balance of bone formation by osteoblasts and bone resorption by osteoclasts. we found that compounds from herbal medicine, Invigorate the Spleen and Tonify the Kidney Formula (ISTKF) accelerates fracture healing. Identification of the active ingredients in ISFKF and the mechanisms of fracture healing involved was carried out. Experimental approach: Using Pax7-Cre;β-catenin conditional knockout(cKO) mice, the mechanisms involved in promoting fracture healing were assessed by looking at the fracture site and its surrounding muscle tissue, using various experiments to analyze the signaling involved. The key molecules and compounds involved in this fracture-promoting effect were identified by HPLC analysis. Key results: Histopathological staining of muscles and micro-CT of bone revealed that β-catenin knockout in skeletal muscle satellite cells (SMSCs) gives rise to sarcopenia and osteopenia, and ISTKF significantly promoted muscle firmness and also increased proliferation and osteogenic differentiation of SMSCs. ISTKF inhibits the significant decrease in bone mass and the destruction of bone microstructure in Pax7-Cre;β-catenin cKO mice. ISTKF mediates the β-catenin signaling pathway to mobilize SMSCs to migrate to the fracture site, promotes the osteogenic differentiation of SMSCs, and promotes the activity of cartilage and osteoblasts at the OPF site. When β-catenin is promoted by ISTKF, it promotes skeletal muscle fiber remodeling and fractures healing. Conclusion and implications: These results provided the first practical evidence for ISTKF-mediated regulation of SMSCs via β-catenin to promote fracture healing with clinical implications that would aid in the treatment of delayed healing and nonunion of fractures.