POS0041 THE GASOTRANSMITTER HYDROGEN SULFIDE (H2S) IS PROTECTIVE AGAINST CALCIFIC TENDINOPATHY (CT)

Background: Pathological (or heterotopic) calcification is the deposition of calcium-containing crystals in soft tissues that normally do not calcify. The these tendons such as rotator cuff and Achilles tendon known calcific tendinopathy (CT). CT a painful condition, which increases rupture rate leads to disability. Objectives: To understand what inhibits calcification, order provide new strategies treat condition for existing therapies are ineffective. Methods: We investigated role gasotransmitter hydrogen sulfide (H 2 S), particular H S-producing enzyme cystathionine γ-lyase (CSE) CT. In vitro , we induced tenocytes from WT CSE KO mice or treated with different S donors. vivo, was assessed surgery-induced murine model (tenotomy tendon) spontaneous (aging). Samples obtained patients were also analyzed. investigate underlying mechanisms CSE-H effect, focused on bone morphogenic proteins (BMPs) pathway. additionally explored if altered extracellular matrix (ECM) organization, due lysyl oxidase (LOX) activity aberrant collagen-crosslinks, could be involved this context, studied affect LOX expression activity. Results: tenocyte inhibited by exogenous S-donors, while it exacerbated tenocytes. protective confirmed vivo. aged mice, microtomography analysis revealed compared WT. CT, an inverse correlation between operated seen over time. Similarly, inversed found human samples. Reduced exposed accompanied decreased genes coding BMP2, BMP4 activation BMP signaling pathway (pSMAD1/5/8). On contrary, BMPs BMPs-pathway next whether ECM disorganization play Tenocytes cultured media pan-inhibitor oxidases (LOX, LOXL1-4) β-aminopropionitrile (BAPN) showed calcification. This pointed potential beneficial inhibition, therefore By LOXs gene calcifying much higher (4-fold) LOX, LOL2 LOXL4 Moreover, S-donors Altogether, results suggest lead activity, excessive collagen cross-links ECM, ultimately Further experiments ongoing prove hypotheses. Conclusion: targeting production CSE, supplying S-donor, therapeutic relevance pathological context can modify its disease course. anti-mineralizing effect both inhibition suppression abnormal Disclosure Interests: None declared.