Hyaluronan-Based Gel Promotes Human Dental Pulp Stem Cells Bone Differentiation by Activating YAP/TAZ Pathway
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
Affiliations
Marcella La Noce
Department of Experimental Medicine, Section of Biotechnology, Molecular Medicine and Medical Histology, University of Campania “L. Vanvitelli”, Via L. de Crecchio 7, 80138 Naples, Italy
Antonietta Stellavato
Department of Experimental Medicine, Section of Biotechnology, Molecular Medicine and Medical Histology, University of Campania “L. Vanvitelli”, Via L. de Crecchio 7, 80138 Naples, Italy
Valentina Vassallo
Department of Experimental Medicine, Section of Biotechnology, Molecular Medicine and Medical Histology, University of Campania “L. Vanvitelli”, Via L. de Crecchio 7, 80138 Naples, Italy
Marcella Cammarota
Department of Experimental Medicine, Section of Biotechnology, Molecular Medicine and Medical Histology, University of Campania “L. Vanvitelli”, Via L. de Crecchio 7, 80138 Naples, Italy
Luigi Laino
Multidisciplinary Department of Medical-Surgical and Dental Specialties, University of Campania “L. Vanvitelli”, Via L. de Crecchio 6, 80138 Naples, Italy
Vincenzo Desiderio
Department of Experimental Medicine, Section of Biotechnology, Molecular Medicine and Medical Histology, University of Campania “L. Vanvitelli”, Via L. de Crecchio 7, 80138 Naples, Italy
Vitale Del Vecchio
Department of Experimental Medicine, Section of Biotechnology, Molecular Medicine and Medical Histology, University of Campania “L. Vanvitelli”, Via L. de Crecchio 7, 80138 Naples, Italy
Giovanni Francesco Nicoletti
Multidisciplinary Department of Medical-Surgical and Dental Specialties, University of Campania “L. Vanvitelli”, Via L. de Crecchio 6, 80138 Naples, Italy
Virginia Tirino
Department of Experimental Medicine, Section of Biotechnology, Molecular Medicine and Medical Histology, University of Campania “L. Vanvitelli”, Via L. de Crecchio 7, 80138 Naples, Italy
Gianpaolo Papaccio
Department of Experimental Medicine, Section of Biotechnology, Molecular Medicine and Medical Histology, University of Campania “L. Vanvitelli”, Via L. de Crecchio 7, 80138 Naples, Italy
Chiara Schiraldi
Department of Experimental Medicine, Section of Biotechnology, Molecular Medicine and Medical Histology, University of Campania “L. Vanvitelli”, Via L. de Crecchio 7, 80138 Naples, Italy
Giuseppe Andrea Ferraro
Multidisciplinary Department of Medical-Surgical and Dental Specialties, University of Campania “L. Vanvitelli”, Via L. de Crecchio 6, 80138 Naples, Italy
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.
