Wound-healing Processes After Pulpotomy in the Pulp Tissue of Type 1 Diabetes Mellitus Model Rats

Rosa Baldeon-Gutierrez; Naoto Ohkura; Kunihiko Yoshiba; Nagako Yoshiba; Aiko Tohma; Ryosuke Takeuchi; Razi Saifullah Ibn Belal; Naoki Edanami; Shintaro Takahara; Susan Gomez-Kasimoto; Takako Ida; Yuichiro Noiri

doi:10.1016/j.joen.2023.10.016

Wound-healing Processes After Pulpotomy in the Pulp Tissue of Type 1 Diabetes Mellitus Model Rats

J Endod. 2024 Feb;50(2):196-204. doi: 10.1016/j.joen.2023.10.016. Epub 2023 Nov 7.

Affiliations

¹ Division of Cariology, Operative Dentistry and Endodontics, Department of Oral Health Science, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
² Division of Cariology, Operative Dentistry and Endodontics, Department of Oral Health Science, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan. Electronic address: ohkura@dent.niigata-u.ac.jp.
³ Division of Oral Science for Health Promotion, Department of Oral Health and Welfare, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.

PMID: 37939821
DOI: 10.1016/j.joen.2023.10.016

Abstract

Introduction: Patients with type 1 diabetes mellitus (DM1) tend to have delayed wound healing, even in the pulp tissue. We hypothesized that hyperglycemia affects odontoblast-like cell (OLC) differentiation and is involved in macrophage polarization. Accordingly, we evaluated dental pulp stem cell differentiation and macrophage phenotypes after pulpotomy.

Methods: After modifying DM1 rat models by streptozotocin, 8-week-old rats' upper left first molars were pulpotomized with mineral trioxide aggregate. Meanwhile, the control group was administered saline. Immunohistochemical localization of nestin, osteopontin, α-smooth muscles (α-SMAs), and CD68 (pan-macrophage marker) was conducted 7 days after pulpotomy. The OLC differentiation stage was determined using double immunofluorescence of nestin and α-SMA. Double immunofluorescence of CD68 and iNOS was counted as M1 macrophages and CD68 and CD206 as M2 macrophages. Proliferating cell nuclear antigen and Thy-1 (CD90) were evaluated by immunofluorescence.

Results: In DM1 rats, the reparative dentin bridge was not complete; however, the osteopontin-positive area did not differ significantly from that in controls. Proliferating cell nuclear antigen, indicative of cell proliferation, increased in positive cells in DM1 rats compared with controls. Double-positive cells for α-SMA and nestin indicated many immature OLCs in DM1. CD90 was positive only in controls. CD68-positive cells, especially M1 macrophages, were increased in DM1 rats, allowing the inflammatory stage to continue 7 days after pulpotomy.

Conclusions: The condition of DM1 model rats can interfere at various stages of the wound healing process, altering OLC differentiation and macrophage polarization. These findings highlight the importance of normal blood glucose concentrations during pulp wound healing.

Keywords: Dental pulp healing; odontoblast-like cells; pulpotomy; reparative dentin; type 1 diabetes mellitus.

MeSH terms

Animals
Dental Pulp
Diabetes Mellitus, Type 1*
Humans
Nestin
Osteopontin
Proliferating Cell Nuclear Antigen
Pulpotomy*
Rats
Rats, Wistar
Wound Healing

Substances

Nestin
Osteopontin
Proliferating Cell Nuclear Antigen