Jiawei yanghe decoction alleviates osteoporotic osteoarthritis by promoting MSC osteogenic differentiation and homing via ITGB6/TGF-β/CXCR4 pathway.

BACKGROUND

Osteoporotic osteoarthritis (OPOA), a distinct subtype of osteoarthritis (OA), has imposed a significant health and economic burden worldwide. However, mechanistic studies and therapeutic strategies for this disease remain in the exploratory stage.

PURPOSE: This study aimed to investigate the specific molecular mechanisms by which osteoporosis (OP) exacerbates OA progression through accelerated subchondral bone (SB) sclerosis and the potential of Jiawei Yanghe Decoction (JWYHD) in treating OPOA.

METHODS

Key genes in the progression of OPOA were investigated through human clinical sample studies, GEO database analysis, and RNA-seq. The OPOA mouse model was established by a combination of OVX and DMM, with JWYHD administered at different concentrations. In vivo, the pathological status of OPOA and the therapeutic effects of JWYHD were evaluated using behavioral tests, micro-CT, and histopathological examinations. In vitro, the osteogenic differentiation and migration capabilities of mesenchymal stem cells (MSC) were assessed by WB, qRT-PCR, Transwell assays, wound healing assays, and IF co-staining.

RESULTS

ITGB6/TGF-β plays a vital role in the pathogenesis of OPOA. A novel concept, the 'Diaphysis-Epiphysis paradox', is hereby proposed, providing a new theoretical framework for research into the pathomechanisms of OPOA from the perspective of abnormal bone mass distribution. By protecting cartilage, regulating the balance of bone mass, and modulating the migration of MSC, JWYHD improves cartilage degeneration and bone mass distribution abnormalities caused by OPOA in an all-around manner.

CONCLUSION

Abnormal migration and osteogenic differentiation disorders of MSC accelerate OPOA progression. JWYHD achieved bidirectional regulation of OPOA through ITGB6/TGF-β/β-catenin and CXCL12/CXCR4 multiple signaling pathways.