Role of chondroitin sulfate in the developmental and healing process of the dental pulp in mice

Ida‐Yonemochi, Hiroko; Takeuchi, Kosei; Ohshima, Hayato

doi:10.1007/s00441-022-03575-3

Cited by 5 publications

(2 citation statements)

References 42 publications

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“…The copyright holder for this preprint this version posted April 2, 2023. ; https://doi.org/10.1101/2023.03.30.534919 doi: bioRxiv preprint 20 Chondroitin sulfate is also indicated to be involved in tooth development (Ida-Yonemochi et al, 2022). Our results regarding the diminished odontoblast differentiation and dentin matrix production in Slc26a2-KO-△exon2 mice are consistent with the phenotype of transgenic mice with a genetic modification of sulfated GAGs.…”

Section: Discussionsupporting

confidence: 84%

SLC26A2-mediated sulfate metabolism is essential for the tooth development

Yoshida

Inubushi

Yokoyama

et al. 2023

Preprint

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The sulfate transporter gene SLC26A2 is responsible for diastrophic dysplasia, which represents skeletal dysplasia in humans. This highlights the importance of sulfate metabolism in skeletal formation. SLC26A2-related chondrodysplasia is also known to exhibit abnormalities in craniofacial and tooth development. Although the function of SLC26A2 in mammals has been investigated using genetic mouse models, the essential role of SLC26A2 during craniofacial and tooth development has not been elucidated. In this study, we demonstrate the pivotal roles of SLC26A2-mediated sulfate metabolism during tooth development. Analysis of Slc26a2 expression reveals that it is predominantly expressed in dental tissues, including odontoblasts and ameloblasts, during tooth development. Slc26a2 knockout mice (Slc26a2-KO-Δexon2) exhibit a retrognathic upper jaw, small upper incisors, and hypoplasia of upper molars. Additionally, upper incisors and molars in Slc26a2-KO-Δexon2 mice display flattened odontoblasts and nuclei that lack intracellular polarity. In contrast, tooth phenotype is not remarkable in lower incisors and molars. Furthermore, the expression of odontoblast differentiation markers, Dspp and Dmp1, is significantly decreased in the upper molars of Slc26a2-deficient mice. Ex vivo organ culture of tooth germs by implantation of Slc26a2-deficient tooth germs under the kidney capsule reveals hypoplasia of the dentin matrix as well as tooth root shortening. In vitro studies using human dental pulp stem cells (hDPSCs) show that the expression levels of Dspp and Dmp1 in shSlc26a2 knockdown cells are significantly decreased compared to control cells. Collectively, our data demonstrate that SLC26A2-mediated sulfate metabolism is essential for tooth development. This study may provide insight into the mechanisms underlying tooth abnormalities in patients with recessively inherited chondrodysplasias caused by mutations in the SLC26A2 gene.

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Section: Discussionsupporting

confidence: 84%

SLC26A2-mediated sulfate metabolism is essential for the tooth development

Yoshida

Inubushi

Yokoyama

et al. 2023

Preprint

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“…Glycosaminoglycans (GAGs) are ubiquitous, vital polysaccharides found in both vertebrate and invertebrate animals (1). GAGs are typically found covalently bound to relatively small protein cores, forming a proteoglycan (PG) (2) and possess numerous important roles, ranging from tissue structure and stability (3,4) through to cell signalling (5), which in turn modulates numerous biological processes including cell growth and proliferation (6), cell adhesion (7), wound repair (8,9) and pathogenic invasion (10)(11)(12)(13). GAGs consist of four major subtypes, namely hyaluronic acid (HA), keratan sulphate (KS), heparan sulphate (HS), and chondroitin sulphate (CS) and are comprised of a disaccharide repeat, containing a hexoseamine-acetate (HexNAc; glucosamine (GlcNAc) for HS and HA, galactoseamine (GalNAc) for CS and KS) and a uronic acid (GalA or iduronic acid (IdoA); just Gal for KS) residue.…”

Section: Introductionmentioning

confidence: 99%

Mass spectrometry imaging with trapped ion mobility spectrometry (TIMS) facilitates spatially resolved chondroitin, dermatan and hyaluronan glycosaminoglycan (GAG) oligosaccharide analysis in situ.

Devlin,

Green,

Takats

2024

Preprint

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The spatial analysis of glycosaminoglycans (GAGs) by type and sulphation state is currently unobtainable. Here, we describe a mass spectrometry imaging (MSI) approach which enables the detection, identification, localisation and profiling of GAG oligosaccharides directly from retinal tissue. With in situ treatment of tissues with relevant chondroitinase enzymes, we liberate and spatially resolve chondroitin, dermatan and hyaluronan disaccharides through to hexasaccharides directly from tissue sections. We demonstrate, through the use of trapped ion mobility spectrometry (TIMS), that it is possible to both separate and semi-quantify isomeric GAG oligosaccharide ions across histologically relevant regions. Hence, we describe the first step towards the spatially resolved analysis of multiple GAGs and their oligosaccharide sulphation state(s) in tissues.

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