ANALISI DI NUOVI MARCATORI CELLULARI E MOLECOLARI PER LA SPONDILITE ANCHILOSANTE

Objective. Here we investigated spontaneous and induced osteoclastogenesis in peripheral blood mononuclear cells (PBMCs) from ankylosing spondylitis (AS) patients, in order to explore the relation between osteoclastogenesis and disease activity. In addition, in order to explore functional characteristics of AS osteoclasts (OCs), we tested their susceptibility to undergo apoptosis investigating their response to Emblica officinalis plant extracts, previously characterized by us as apoptotic inducer in OCs. Methods. PBMCs from healthy individuals and AS patients were cultured with or without osteoclastogenic inducers, stained for tartrate-resistant acid phosphatase (TRAP), and immunostained for Bcl-XL, Survivin and Bim proteins. After treatment with E. officinalis extracts, OCs were subjected to TUNEL test for measuring apoptosis. Disease activity was measured by Ankylosing Spondylitis Disease Actvity Score-CRP (ASDAS-CRP) and magnetic resonance imaging. Results. We found that PBMCs from AS are more susceptible to spontaneous osteoclastogenesis than the PBMCs from control samples, and that the osteoclastogenic potential was significantly associated with high ASDAS among AS patients with bone marrow edema. In addition, after treatment with E. officinalis extracts normal OCs underwent apoptosis, but OCs from AS patients showed a strong resistance to apoptotic stimulus. We found that OCs from AS patients, unlike OCs from healthy individuals, express high levels of survival signals including Bcl-XL and Survivin, but do not express Bim proapoptotic protein. Conclusion. Our data demonstrate that AS OCs present qualitative peculiarities: this may help in identifying an effective strategy to prevent bone changes in AS.