Inhibition of sphingomyelinase blocks the recruitment of alkaline phosphatase to mineralization-competent matrix vesicles.

Hayann, Larwsk; Cominal, Juçara G; Lima, Iara S; Patricio, Miguel Rocha; Mello, Maryanne T; Andrilli, Luiz H S; de Sousa, Juliana R S; Sorgi, Carlos A et al. · Bone · 2026

basic_science · Level V

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Abstract

Mineralizing cells release extracellular vehicles (EVs), including mineralization-competent matrix vesicles (MVs), that bind to collagen and initiate mineralization. MVs budding from lipid-raft-rich domains contain enzymes such as tissue-nonspecific alkaline phosphatase (TNAP), which is crucial for mineral formation. This study examined the effect of inhibiting neutral sphingomyelinase (SMase) on extracellular vesicle (EV) and MV release, and TNAP recruitment to MVs. Our results suggest that SMase inhibition significantly reduced TNAP recruitment and phosphomonohydrase activity in MVs as well as altered MV topography and morphology due to changes in the lipid profile.

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