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-CreERT2/+;β-cateninfx/fx
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-CreERT2/+;β-cateninfx/fx
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.