Alexander Patera Nugraha, Guang Hong, Kunhua Yang, Ida Bagus Narmada, Fedik Abdul Rantam, Diah Savitri Ernawati, I Gusti Aju Wahju Ardani, Adya Pramusita, Nurul Aisyah Rizky Putranti, Naora Dewi Rahma Fadzila, Al Zayyan Shenaya Aurora, Reisya Irfanny Farizaldi, Muhammad Luthfi, Putri Cahaya Situmorang, Wibi Riawan, Kotaro Tanimoto
Background/purpose Gingival mesenchymal stem cells (GMSC) show promising qualities in immunoregulation, immunomodulation in regeneration of periodontal tissue during orthodontic tooth movement (OTM). This study aimed to elucidate allogenous GMSC normoxia and hypoxic preconditioning transplantation in the OTM model using New Zealand rabbits ( Oryctolagus cuniculus ) by examining nuclear factor kappa beta (NF-κB), tumour necrosis factor-alpha (TNF-α), nuclear factor associated T-cell-1 (NFATc1), Runt-related transcription factor 2 (RUNX2), Osteocalcin. Materials and methods Four groups were established from forty-eight, healthy, young male rabbits divided into the following respective groups: p1: normoxic GMSC transplantation with OTM, p2: hypoxic GMSC transplantation with OTM, k2: OTM only, and K1: phosphate buffered saline (PBS) only. In order to advance the mandibular first molar mesially, a fixed orthodontic appliance was applied. The rabbit was transplanted with 106 hypoxic or normoxic GMSC in 50 μl of PBS into afflicted gingiva after one day of OTM. All experimental animals were sacrificed on days 7, 14, and 28. Furthermore, mandibular tissue was isolated for the sample to examine NFKβ, TNF-α, NFATc1, osteocalcin, RUNX2 expression, and OTM rate. Results There was a considerable increase in OTM rate, osteocalcin and RUNX2 expression in P2 on day 28 with significantly different between groups. In contrast to other groups, the P2 group's expression of NFKβ, TNF-α, and NFATc1 was considerably lower on day 28 in the tension side of the alveolar bone ( P ≤ 0.05). Conclusion GMSC hypoxia-preconditioning transplantation increases the OTM rate through the RUNX2-osteocalcin-OTM rate stimulation pathway in rabbits ( O. cunniculus ). © 2026 Association for Dental Sciences of the Republic of China.
Dental Regenerative Research Group, Department of Orthodontics, Faculty of Dental Medicine, Universitas Airlangga, Surabaya, Indonesia; Division for Globalization Initiative, Liaison Center for Innovative Dentistry, Graduate School of Dentistry, Tohoku University, Sendai, Japan; Virology and Immunology Laboratory, Microbiology Department, Faculty of Veterinary Medicine, Universitas Airlangga, Surabaya, Indonesia; Department of Oral Medicine, Faculty of Dental Medicine, Universitas Airlangga, Surabaya, Indonesia; Department of Oral Biology, Faculty of Dental Medicine, Universitas Airlangga, Surabaya, Indonesia; Biology Study Program, Faculty of Mathematics and Natural Sciences, Universitas Sumatera Utara, Medan, Indonesia; Department of Biomolecular Biochemistry, Faculty of Medicine, Universitas Brawijaya, Malang, Indonesia; Department of Orthodontics and Craniofacial Developmental Biology, Hiroshima University Graduate School of Biomedical and Health Sciences, Hiroshima, Japan
