Abstract
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.
Highlights
Hyaluronic acid (HA) is a key component of extracellular matrix (ECM) in the majority of human tissues [1].It interacts with other macromolecules and plays a predominant role in tissue morphogenesis, cell migration, differentiation, and adhesion [2].HA structure consists of repeated disaccharide unit of N-acetyl-glucosamine and glucuronic acid, linked through a betaglycosidc bond [3].what we define as hyaluronic acid is not a single and unique molecule with distinct characteristics, but rather a family of macromolecules with different molecular weight and biological activity [4]
We found that hybrid cooperative complexes (HCC) improves osteoblastic differentiation of human dental pulp stem cells (hDPSCs) via activation of the yes-associated protein (YAP)/transcriptional co-activator with PDZ-binding motif (TAZ) pathway
We found that HCC promoted CD44 expression in specific areas of hDPSCs membrane, suggesting that it binds to CD44 with greater efficiency than other formulations for which the CD44 distribution was not homogeneous
Summary
Hyaluronic acid (HA) is a key component of extracellular matrix (ECM) in the majority of human tissues [1].It interacts with other macromolecules and plays a predominant role in tissue morphogenesis, cell migration, differentiation, and adhesion [2].HA structure consists of repeated disaccharide unit of N-acetyl-glucosamine and glucuronic acid, linked through a betaglycosidc bond [3].what we define as hyaluronic acid is not a single and unique molecule with distinct characteristics, but rather a family of macromolecules with different molecular weight and biological activity [4]. Hyaluronic acid (HA) is a key component of extracellular matrix (ECM) in the majority of human tissues [1]. It interacts with other macromolecules and plays a predominant role in tissue morphogenesis, cell migration, differentiation, and adhesion [2]. What we define as hyaluronic acid is not a single and unique molecule with distinct characteristics, but rather a family of macromolecules with different molecular weight and biological activity [4]. 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. 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
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