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


Chondroitin sulfate proteoglycan (CSPG), one of the major extracellular matrices, plays an important part in organogenesis. Its core protein and chondroitin sulfate (CS) chain have a specific biological function. To elucidate the role of CS in the developmental and healing process of the dental pulp, we performed an experimental tooth replantation in CS N-acethylgalactosaminyltransferase-1 (T1) gene knockout (KO) mice. We also performed cell proliferation assay and qRT-PCR analysis for the WT and T1KO primary dental pulp cells using T1-siRNA technique and external CS. During tooth development, CS was diffusely expressed in the dental papilla, and with dental pulp maturation, CS disappeared from the differentiated areas, including the odontoblasts. In fully developed molars, CS was restricted to the root apex region colocalizing with Gli1-positive cells. In the healing process after tooth replantation, CD31-positive cells accumulated in the CS-positive stroma in WT molars. In T1KO molars, the appearance of Ki67- and Gli1-positive cells in the dental pulp was significantly fewer than in WT molars in the early healing stage, and collagen I-positive reparative dentin formation was not obvious in T1KO mice. In primary culture experiments, siRNA knockdown of T1 gene significantly suppressed cell proliferation in WT dental pulp cells, and the mRNA expression of cyclin D1 and CD31 was significantly upregulated by external CS in T1KO dental pulp cells. These results suggest that CS is involved in the cell proliferation and functional differentiation of dental pulp constituent cells, including vascular cells, in the healing process of dental pulp tissue after tooth injury.

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This work was supported by Grant-in-Aid for Scientific Research (C) (no. 26462777 and 18K09505 to H.I.-Y.) from the Japan Society for the Promotion of Science, Japan.

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Correspondence to Hiroko Ida-Yonemochi.

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All experiments complied with the guidelines by the Ministry of Education, Culture, Sports, Science and Technology, the Ministry of the Environment, and the Science Council of Japan and were carried out in accordance with the Act on Welfare and Management of Animals. All the animal experiments were conducted in compliance with the protocol, which was reviewed by the Institutional Animal Care and Use Committee, and were approved by the President of Niigata University (Permit Number: #28 Niigata Univ. Res. 42–9).

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Ida-Yonemochi, H., Takeuchi, K. & Ohshima, H. Role of chondroitin sulfate in the developmental and healing process of the dental pulp in mice. Cell Tissue Res 388, 133–148 (2022).

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  • Chondroitin sulfate
  • Heparan sulfate
  • Dental pulp
  • Tooth replantation
  • Vessels