LIPUS accelerates bone regeneration via HDAC6-mediated ciliogenesis

Area of Science:

• Biomedical Engineering
• Regenerative Medicine
• Orthopedics

Background:

• Delayed fracture union and nonunion are significant clinical challenges.
• Low-intensity pulsed ultrasound (LIPUS) is known to stimulate bone regeneration, but its mechanism remains unclear.
• Understanding LIPUS's mechanism is crucial for optimizing its clinical application in bone repair.

Purpose of the Study:

• To elucidate the mechanism by which LIPUS promotes bone regeneration.
• To investigate the role of periosteal cell fate and ciliogenesis in LIPUS-mediated bone repair.
• To identify HDAC6 as a potential target for LIPUS-based bone regenerative strategies.

Main Methods:

• Generation of transgenic mice to study periosteal cells and ciliated cells under LIPUS.
• In vitro isolation and culture of periosteal cells to assess LIPUS effects.
• Investigation of the relationship between LIPUS, HDAC6, and ciliogenesis in osteogenic differentiation.
• Assessment of femoral bone defect regeneration and osteogenic differentiation of Prrx1+ cells.

Main Results:

• LIPUS significantly promoted femoral bone defect regeneration and enhanced osteogenic differentiation of Prrx1+ cells.
• Knockdown of primary cilia in Prrx1+ cells weakened the pro-regenerative effects of LIPUS.
• LIPUS stimulated the formation of primary cilia in Prrx1+ cells within the bone defect microenvironment.
• In vitro studies confirmed that LIPUS enhances osteogenic differentiation via HDAC6-mediated ciliogenesis.

Conclusions:

• LIPUS promotes osteogenic differentiation of Prrx1+ cells, thereby stimulating bone regeneration.
• LIPUS inhibits HDAC6 expression, leading to an increased prevalence of primary cilia in Prrx1+ cells.
• HDAC6-mediated ciliogenesis is the primary mechanism through which LIPUS enhances osteogenic differentiation and bone regeneration.