Spondyloarthritis & psoriatic arthritis

Piezo1-mediated mechanotransduction promotes entheseal pathological new bone formation in ankylosing spondylitis

Ann Rheum DisPublished Mechanistic study

Authors' conclusion

Piezo1-mediated mechanotransduction promotes entheseal pathological new bone formation through CaMKII signalling in AS.

Study context

Population
Spinal ligament tissues from patients with ankylosing spondylitis (AS) and non-AS controls; collagen antibody-induced arthritis animal models; entheseal osteo-chondral lineage cells
Participants
14 vs 14
Comparison
AS vs non-AS controls; Piezo1 inhibition or activation in animal models
  • ASn = 14
  • Non-AS controlsn = 14reference
Methodological detailsbulk RNA sequencing, collagen antibody-induced arthritis models, pharmacological inhibition and genetic ablation of Piezo1, in vitro cell culture
  • Bulk RNA sequencing
  • Collagen antibody-induced arthritis models
  • Pharmacological inhibition and genetic ablation of Piezo1
  • In vitro cell culture

Main finding

As reported in the abstract

  • Piezo1 aberrantly upregulated in ligaments and entheseal tissues from patients with AS and animal models
  • Pharmaceutical and genetic inhibition of Piezo1 attenuated, while activation of Piezo1 promoted, pathological new bone formation
  • Activation of CaMKII signalling essential for Piezo1-mediated mechanotransduction
  • Piezo1 upregulated by AS-associated inflammatory cytokines

Original publication

Piezo1-mediated mechanotransduction promotes entheseal pathological new bone formation in ankylosing spondylitis. Ann Rheum Dis. Published 21 December 2022. doi:10.1136/ard-2022-223428

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