Hyaluronan-Based Gel Promotes Human Dental Pulp Stem Cells Bone Differentiation by Activating YAP/TAZ Pathway

Background: Hyaluronans exist in different forms, accordingly with molecular weight and degree of crosslinking. Here, we tested the capability to induce osteogenic differentiation in hDPSCs (human dental pulp stem cells) of three hyaluronans forms: linear pharmaceutical-grade hyaluronans at high and...

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Autores principales: Marcella La Noce, Antonietta Stellavato, Valentina Vassallo, Marcella Cammarota, Luigi Laino, Vincenzo Desiderio, Vitale Del Vecchio, Giovanni Francesco Nicoletti, Virginia Tirino, Gianpaolo Papaccio, Chiara Schiraldi, Giuseppe Andrea Ferraro
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Publicado: MDPI AG 2021
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spelling oai:doaj.org-article:05ac15be70454c1d978d35f00df444072021-11-25T17:08:41ZHyaluronan-Based Gel Promotes Human Dental Pulp Stem Cells Bone Differentiation by Activating YAP/TAZ Pathway10.3390/cells101128992073-4409https://doaj.org/article/05ac15be70454c1d978d35f00df444072021-10-01T00:00:00Zhttps://www.mdpi.com/2073-4409/10/11/2899https://doaj.org/toc/2073-4409Background: Hyaluronans exist in different forms, accordingly with molecular weight and degree of crosslinking. Here, we tested the capability to induce osteogenic differentiation in hDPSCs (human dental pulp stem cells) of three hyaluronans forms: linear pharmaceutical-grade hyaluronans at high and (HHA) low molecular weight (LHA) and hybrid cooperative complexes (HCC), containing both sizes. Methods: hDPSCs were treated with HHA, LHA, HCC for 7, 14 and 21 days. The effects of hyaluronans on osteogenic differentiation were evaluated by qRT-PCR and WB of osteogenic markers and by Alizarin Red S staining. To identify the involved pathway, CD44 was analyzed by immunofluorescence, and YAP/TAZ expression was measured by qRT-PCR. Moreover, YAP/TAZ inhibitor-1 was used, and the loss of function of YAP/TAZ was evaluated by qRT-PCR, WB and immunofluorescence. Results: We showed that all hyaluronans improves osteogenesis. Among these, HCC is the main inducer of osteogenesis, along with overexpression of bone related markers and upregulating CD44. We also found that this biological process is subordinate to the activation of YAP/TAZ pathway. Conclusions: We found that HA’s molecular weight can have a relevant impact on HA performance for bone regeneration, and we unveil a new molecular mechanism by which HA acts on stem cells.Marcella La NoceAntonietta StellavatoValentina VassalloMarcella CammarotaLuigi LainoVincenzo DesiderioVitale Del VecchioGiovanni Francesco NicolettiVirginia TirinoGianpaolo PapaccioChiara SchiraldiGiuseppe Andrea FerraroMDPI AGarticlehyaluronic aciddental pulp stem cellsosteogenic differentiationYAP/TAZ pathwayBiology (General)QH301-705.5ENCells, Vol 10, Iss 2899, p 2899 (2021)
institution DOAJ
collection DOAJ
language EN
topic hyaluronic acid
dental pulp stem cells
osteogenic differentiation
YAP/TAZ pathway
Biology (General)
QH301-705.5
spellingShingle hyaluronic acid
dental pulp stem cells
osteogenic differentiation
YAP/TAZ pathway
Biology (General)
QH301-705.5
Marcella La Noce
Antonietta Stellavato
Valentina Vassallo
Marcella Cammarota
Luigi Laino
Vincenzo Desiderio
Vitale Del Vecchio
Giovanni Francesco Nicoletti
Virginia Tirino
Gianpaolo Papaccio
Chiara Schiraldi
Giuseppe Andrea Ferraro
Hyaluronan-Based Gel Promotes Human Dental Pulp Stem Cells Bone Differentiation by Activating YAP/TAZ Pathway
description Background: Hyaluronans exist in different forms, accordingly with molecular weight and degree of crosslinking. Here, we tested the capability to induce osteogenic differentiation in hDPSCs (human dental pulp stem cells) of three hyaluronans forms: linear pharmaceutical-grade hyaluronans at high and (HHA) low molecular weight (LHA) and hybrid cooperative complexes (HCC), containing both sizes. Methods: hDPSCs were treated with HHA, LHA, HCC for 7, 14 and 21 days. The effects of hyaluronans on osteogenic differentiation were evaluated by qRT-PCR and WB of osteogenic markers and by Alizarin Red S staining. To identify the involved pathway, CD44 was analyzed by immunofluorescence, and YAP/TAZ expression was measured by qRT-PCR. Moreover, YAP/TAZ inhibitor-1 was used, and the loss of function of YAP/TAZ was evaluated by qRT-PCR, WB and immunofluorescence. Results: We showed that all hyaluronans improves osteogenesis. Among these, HCC is the main inducer of osteogenesis, along with overexpression of bone related markers and upregulating CD44. We also found that this biological process is subordinate to the activation of YAP/TAZ pathway. Conclusions: We found that HA’s molecular weight can have a relevant impact on HA performance for bone regeneration, and we unveil a new molecular mechanism by which HA acts on stem cells.
format article
author Marcella La Noce
Antonietta Stellavato
Valentina Vassallo
Marcella Cammarota
Luigi Laino
Vincenzo Desiderio
Vitale Del Vecchio
Giovanni Francesco Nicoletti
Virginia Tirino
Gianpaolo Papaccio
Chiara Schiraldi
Giuseppe Andrea Ferraro
author_facet Marcella La Noce
Antonietta Stellavato
Valentina Vassallo
Marcella Cammarota
Luigi Laino
Vincenzo Desiderio
Vitale Del Vecchio
Giovanni Francesco Nicoletti
Virginia Tirino
Gianpaolo Papaccio
Chiara Schiraldi
Giuseppe Andrea Ferraro
author_sort Marcella La Noce
title Hyaluronan-Based Gel Promotes Human Dental Pulp Stem Cells Bone Differentiation by Activating YAP/TAZ Pathway
title_short Hyaluronan-Based Gel Promotes Human Dental Pulp Stem Cells Bone Differentiation by Activating YAP/TAZ Pathway
title_full Hyaluronan-Based Gel Promotes Human Dental Pulp Stem Cells Bone Differentiation by Activating YAP/TAZ Pathway
title_fullStr Hyaluronan-Based Gel Promotes Human Dental Pulp Stem Cells Bone Differentiation by Activating YAP/TAZ Pathway
title_full_unstemmed Hyaluronan-Based Gel Promotes Human Dental Pulp Stem Cells Bone Differentiation by Activating YAP/TAZ Pathway
title_sort hyaluronan-based gel promotes human dental pulp stem cells bone differentiation by activating yap/taz pathway
publisher MDPI AG
publishDate 2021
url https://doaj.org/article/05ac15be70454c1d978d35f00df44407
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