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00925njm 22002777a 4500 dc Castro Vázquez, David author Lamana Rodríguez, Amalia author Arribas Castaño, Paula author Gutiérrez Cañas, Irene author Villanueva Romero, Raúl author Pérez García, Selene author Martínez Mora, María Del Carmen author Juarranz Moratilla, Yasmina author Fernández de Córdoba, Sara author González Álvaro, Isidoro author Gomáriz, Rosa P. author Carrión Caballo, Mar author 2021-12-10 We aimed to evaluate the direct action of VIP on crucial molecules involved in human osteoclast differentiation and function. We also investigated the relationship between VIP serum levels and bone remodeling mediators in early arthritis patients. The expression of VIP receptors and osteoclast gene markers in monocytes and in vitro differentiated osteoclasts was studied by real-time PCR. NFATc1 activity was measured using a TransAM® kit. Osteoclastogenesis was confirmed by quantification of tartrate-resistant acid phosphatase positive multinucleated cells. OsteoAssay® Surface Multiple Well Plate was used to evaluate bone-resorbing activity. The ring-shaped actin cytoskeleton and the VPAC1 and VPAC2 expression were analyzed by immunofluorescence. We described the presence of VIP receptors in monocytes and mature osteoclasts. Osteoclasts that formed in the presence of VIP showed a decreased expression of osteoclast differentiation gene markers and proteolytic enzymes involved in bone resorption. VIP reduced the resorption activity and decreased both β3 integrin expression and actin ring formation. Elevated serum VIP levels in early arthritis patients were associated with lower BMD loss and higher serum OPG concentration. These results demonstrate that VIP exerts an anti-osteoclastogenic action impairing both differentiation and resorption activity mainly through the negative regulation of NFATc1, evidencing its bone-protective effects in humans. Castro Vázquez, D., Lamana Rodríguez, A., Arribas Castaño, P. et al. «The Neuropeptide VIP Limits Human Osteoclastogenesis: Clinical Associations with Bone Metabolism Markers in Patients with Early Arthritis». Biomedicines, vol. 9, n.o 12, diciembre de 2021, p. 1880. Crossref, https://doi.org/10.3390/biomedicines9121880. 10.3390/biomedicines9121880 https://hdl.handle.net/20.500.14352/4899 2227-9059 https://doi.org/10.3390/biomedicines9121880 https://www.mdpi.com/2227-9059/9/12/1880 The Neuropeptide VIP Limits Human Osteoclastogenesis: Clinical Associations with Bone Metabolism Markers in Patients with Early Arthritis