Authors' Reply “Histochemical Assessment of Cementum and Alveolar Bone in <scp> SDT <i>fa</i> / <i>fa</i> </scp> Rat Mimicking Type <scp>II</scp> Diabetes”

We sincerely appreciate the thoughtful and constructive comments provided by Yin et al. (2025) regarding our recent article, “Histochemical Assessment of Cementum and Alveolar Bone in SDT fa/fa Rats Mimicking Type II Diabetes” (Hasegawa et al. 2025). Their insights offer valuable perspectives for deepening the understanding of diabetic periodontal pathology and provide an opportunity to further clarify the objectives, methodology, and interpretations of our study. As noted by the authors, scanning electron microscopy combined with energy-dispersive X-ray spectroscopy (SEM–EDX) is a robust method for characterizing microstructural defects and elemental alterations in cementum. Such analyses would be highly informative within the context of our investigation. Previous SEM-based studies have demonstrated that, relative to non-diabetic periodontitis, affected cementum is generally thinner (Gupta et al. 2013), and the concentrations of select minerals, such as magnesium and copper, are diminished (Barton and Van 1987). In our study, we focused on identifying alterations in the distribution of matrix proteins within cementum, suggesting that such changes may contribute to bacterial invasion and persistent infection. We fully concur that future work should employ SEM–EDX to elucidate ultrastructural and elemental changes in greater detail. We also appreciate the suggestion to incorporate biochemical biomarkers in serum or periodontal tissues. While our investigation primarily focused on histopathological analyses, a combined assessment of bone metabolic markers, such as RANKL/OPG, TRAP, osteocalcin, and PINP, inflammatory cytokines, and advanced glycation end products could help elucidate the mechanisms driving the pathological abnormalities observed in diabetic periodontal tissues. However, as our study employed an animal model with a limited sample size, it was not designed for complex structural equation modeling (SEM) analyses (Cheung et al. 2013; Nascimento et al. 2019), and the prerequisites for such modeling were therefore not met. We agree that, given the multifactorial nature of diabetic periodontitis and the need to integrate diverse parameters—including glycemic control, inflammatory status, and regulators of bone metabolism—SEM offers distinct advantages when applied in appropriately powered clinical studies. In conclusion, we are gratified that our study has generated interest among researchers and clinicians. Our work represents the first detailed histological characterization of diabetic periodontal changes in the SDT fa/fa rat model. We sincerely appreciate the constructive suggestions provided by Yin et al. and look forward to advancing our understanding of this model through the integration of ultrastructural, biochemical, and interventional approaches in subsequent research. Tomoka Hasegawa: conceptualization, methodology, writing – original draft, project administration, data curation, validation, supervision, investigation, writing – review and editing. Mako Sakakibara: data curation, validation, writing – original draft, investigation. Xuanyu Liu: investigation. Mai Haraguchi-Kitakamae: investigation. Weisong Li: investigation. Haoyu Wang: investigation. Yan Shi: investigation. Jiaxin Cui: investigation. Hiromi Hongo: investigation, funding acquisition. Tomomaya Yamamoto: investigation. Miki Abe-Takagi: investigation, funding acquisition. Haruhi Maruoka: investigation, funding acquisition. Hirofumi Miyaji: writing – review and editing. Minqi Li: writing – review and editing. Norio Amizuka: funding acquisition, writing – review and editing. This work was supported by the Japan Society for the Promotion of Science. The authors declare no conflicts of interest.