RT Journal Article
T1 Osteoprotective effects of the neuropeptide VIP: insights from triple cultures of human osteocytes, osteoblasts, and osteoclasts
A1 Castro Vázquez, David
A1 García López, Ivan
A1 Wirsig, Katharina
A1 Arribas Castaño, Paula
A1 Pérez Gomáriz, Rosa María
A1 Martínez Mora, María Del Carmen
A1 Juarranz Moratilla, Yasmina
A1 Bernhardt, Anne
A1 Carrión Caballo, Mar
AB Bone remodelling is a dynamic process of osteoblastic bone formation and osteoclastic bone resorption, regulated by local, paracrine and endocrine factors, in which osteocytes act as orchestrators of bone homeostasis. Among these regulatory factors, the neuropeptide VIP (vasoactive intestinal peptide) has demonstrated osteoprotective effects by inhibiting osteoclastogenesis and promoting osteoblast differentiation. However, its potential role in osteocyte biology remains unexplored. In this study, we investigated the effect of VIP on the differentiation of primary human osteocytes. We describe for the first time the expression of VIP and its receptors during in vitro osteocyte differentiation. Our results show that VIP promotes osteocytogenesis, accompanied by a reduction in the RANKL/OPG ratio, thereby supporting its role as an anti-osteoclastogenic factor. To better mimic the complexity of bone tissue, we performed triple co-cultures of osteoblasts and simultaneously differentiating osteocytes and osteoclasts, in the presence or absence of VIP. Our results confirmed that VIP supports the osteoblast-to-osteocyte transition and promotes an osteoprotective phenotype, characterized by a reduced RANKL/OPG ratio and decreased SOST expression. The downregulation of sclerostin may attenuate osteocyte-mediated inhibitory signalling toward osteoblasts and, in turn, contribute to the reduction of the osteoblastic RANKL/OPG ratio. Collectively, our findings reinforce the anti-osteoclastogenic actions of VIP, supporting its role as a potential osteoprotective factor.
PB Elsevier
SN 1931-5244
YR 2026
FD 2026-04-19
LK https://hdl.handle.net/20.500.14352/136623
UL https://hdl.handle.net/20.500.14352/136623
LA eng
NO Castro-Vazquez, D., García-Lopez, I., Wirsig, K., Arribas-Castaño, P., Gomariz, R. P., Martínez, C., Juarranz, Y., Bernhardt, A., & Carrion, M. (2026). Osteoprotective effects of the neuropeptide VIP: insights from triple cultures of human osteocytes, osteoblasts, and osteoclasts. Translational Research, 292, 40–51. https://doi.org/10.1016/j.trsl.2026.04.004
NO AcknowledgementsWe thank the Genomics and Fluorescence Microscopy Centres of Complutense University for the use of their facilities. We are grateful to all donors and the collaborating clinicians for their participation in this study. We also appreciate the assistance of Isabel Montero, for her assistance with histology techniques.FundingThis research was funded by grants RD24/0007/0014 and RD21/0002/0004 from the Ministerio de Economía y Competitividad (Instituto de Salud Carlos III), co-funded by European regional developmentfund (ERDF) and by the UCM grants PR12/24-31568 and PR12/24-31572. DC-V was awarded with an EMBO Scientific Exchange Grant (SEG 10287). KW was awarded a scholarship funded by and in cooperation with the Saxon Ministry for Higher Education and Arts and the Studentenwerk Dresden.
NO Ministerio de Economía y Competitividad (España)
NO Instituto de Salud Carlos III (España)
NO Universidad Complutense de Madrid
NO Saxon Ministry for Higher Education and Arts
NO Studentenwerk Dresden
DS Docta Complutense
RD 9 may 2026