The Neuropeptide VIP Limits Human Osteoclastogenesis: Clinical Associations with Bone Metabolism Markers in Patients with Early Arthritis

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Castro Vázquez, David and Lamana, Amalia and Arribas Castaño, Paula and Gutiérrez Cañas, Irene and Villanueva Romero, Raúl and Pérez García, Selene and Martínez Mora, Carmen and Juarranz Moratilla, Yasmina and Fernández de Córdoba, Sara and González Álvaro, Isidoro and Gomáriz, Rosa P. and Carrión Caballo, Mar (2021) The Neuropeptide VIP Limits Human Osteoclastogenesis: Clinical Associations with Bone Metabolism Markers in Patients with Early Arthritis. Biomedicines, 9 (12). pp. 1-16. ISSN Electronic: 2227-9059

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Official URL: https://doi.org/10.3390/biomedicines9121880




Abstract

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.


Item Type:Article
Uncontrolled Keywords:VIP; Arthritis; Osteoclastogenesis; Bone erosion; Osteoclast; αvβ3 integrin; Actin cytoskeleton; NFATc1
Subjects:Medical sciences > Medicine > Rheumatology
Medical sciences > Biology > Biochemistry
ID Code:72372
Deposited On:20 May 2022 08:31
Last Modified:14 Jun 2022 10:59

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