Introduction: Pseudoarthrosis remains a serious complication in modern spine surgery. Bone formation is fundamentally driven by mechanical forces. Recently, Piezo 1, a mechanosensitive calcium channel, has been identified as a key force sensor in osteocytes. However, advanced methods to investigate the mechanisms of spinal fusion, particularly Piezo 1-mediated mechanotransduction at the molecular and cellular levels, are still lacking. There has been growing interest in Yoda 1, a Piezo 1 activator, as a potential agent to promote bone formation. In this study, we applied Yoda 1 topically over bone graft in a mouse spinal fusion model, analyzing bone architecture and RNA expression pathways.
Methods: Twelve-week-old female C57BL/6 mice underwent spine fusion surgery. Bone graft from iliac crest donor mice was placed over the decorticated laminae, spanning L2-L4 in recipient mice. A collagen sponge soaked in either Yoda 1 or saline (control) was applied topically to the fusion bed. At 4 weeks post-surgery, spines were harvested, and RNA was extracted using the PureLink RNA Mini Kit for Illumina bulk RNA sequencing. At 8 weeks, samples were harvested for micro-CT scanning (Scanco micro CT 40 system) to assess bone architecture.
Results: Notably, Alox15, a gene associated with osteoporosis, was significantly downregulated in Yoda 1 treated samples, suggesting a potential protective effect against bone resorption. Conversely, Calca, which encodes procalcitonin (PCT), was upregulated in Yoda 1 treated samples. PCT expression in osteoblasts is known to inhibit osteoclastogenesis-related macrophage migration and fusion, indicating a potential mechanism for promoting bone stability in the treated samples. Micro CT analysis at 8 weeks did not reveal statistically significant results, though there was a trend toward increased trabecular number (6.614, SD 0.318 vs. 5.968, SD 0.667 mm⁻¹), trabecular thickness (0.0856, SD 0.0045 vs. 0.0786, SD 0.0071 mm), and bone mineral density (BMD: 407.0, SD 2.95 vs. 375.2, SD 6.31 mg HA/cm³) in Yoda 1-treated mice compared to saline-treated controls.
Conclusion : Yoda 1 treatment appears to enhance trabecular architecture and modulate bone-stability gene pathways in a mouse spinal fusion model. Although micro-CT results were not statistically significant, trends in trabecular number, thickness, and BMD suggest Piezo 1 activation could improve bone quality in spinal fusion.
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