Adya Pramusita, Ida B. Narmada, Ervina R. Winoto, Alida Alida, Fitri D.A. Pratiwi, Labieb F. Zaky, Ari Triwardhani, I.G.A.W. Ardani, Wibi Riawan, Desy Novianti, Nurul A.R. Putranti, Ananda F. Putranto, Tengku N.E.B.T.A. Noor, Alexander P. Nugraha
Objective The mesenchymal stem cell (MSC) secretome has emerged as a promising cell-free approach for modulating bone remodeling, but its effects during the orthodontic relapse phase remain poorly understood. This study investigated the effects of the human umbilical cord-derived MSC (hUC-MSC) secretome on alveolar bone remodeling during orthodontic relapse. Methods Forty-one male Wistar rats were randomly assigned to three groups: negative control (C−), positive control (C+), and secretome-treated relapse group (S). S rats were subjected to submucosal injections of the hUC-MSC secretome, whereas the control groups received submucosal injection of phosphate-buffered saline. Orthodontic force was applied for 14 days to move the maxillary first molars mesially. Relapse began on day 14 after the appliance was removed. A retention device was placed only in C− rats. The rats were sacrificed on days 21 and 28, and the expression levels were assessed for cathepsin K (CTSK), tartrate-resistant acid phosphatase (TRAP), osteoprotegerin, receptor activator of nuclear factor-κB ligand, alkaline phosphatase (ALP), and osteocalcin (OCN) via immunohistochemistry. Results Quantitative analysis demonstrated that the TRAP and CTSK expression levels were significantly lower in S than C−, but remained comparable to those in C+. In addition, the RANKL/OPG ratio was consistently lowest in S at both time points compared with C− and C+. Furthermore, across both observation periods, the expression levels of ALP and OCN were significantly higher in S compared with C−. Conclusion The hUC-MSC secretome may promote a favorable alveolar bone remodeling balance at the tension side during orthodontic relapse by suppressing osteoclastic activity and enhancing osteoblastic activity. © 2026 The Authors.
Dental Regenerative Research Group, Department of Orthodontics, Faculty of Dental Medicine, Universitas Airlangga, East Java, Surabaya, Indonesia; Biomolecular Biochemistry, Faculty of Medicine, Brawijaya University, Malang, Indonesia; Centre of Studies for Periodontology, Faculty of Dentistry, Universiti Teknologi MARA (UiTM), Selangor, Sungai Buloh, Malaysia
