Putri Cahaya Situmorang, Helen Helen, Syafruddin Ilyas, Salomo Hutahaean, Doni Aldo Samuel Siahaan, Ananto Ali Alhasyimi, Muh Ade Artasasta, Wibi Riawan, Khairul Anuar Shariff, Alexander Patera Nugraha
BackgroundHyperglycemia-induced osteolysis is a significant consequence of diabetes mellitus, marked by heightened inflammatory responses, augmented osteoclastogenesis, and compromised osteoblast function. Innovative therapy approaches aimed at inflammatory and cytoprotective mechanisms are essential to avert diabetic bone loss.ObjectiveThis study investigated the synergistic effects of human umbilical cord mesenchymal stem cell (HUC-MSC) secretome and Nanoemulsion Propolis (NEP) on inflammatory responses and protective protein expression in a rat model of hyperglycemia-associated calvarial osteolysis.MethodsMale Wistar rats were categorized into seven groups: control, LPS-induced inflammation, hyperglycemia, a combination of LPS and hyperglycemia, and treatment groups administered HUC-MSC secretome, NEP, or both. Cytokine concentrations (IL-1β, TNF-α, IL-10) were measured using ELISA, whilst NF-κB, IL-6, HSP-70, and HSP-10 expression in calvarial tissue was assessed by immunohistochemistry.ResultsLPS, in conjunction with hyperglycemia, significantly increased pro-inflammatory cytokines and NF-κB activation, reduced IL-10 levels, and inhibited HSP-70 and HSP-10, hence worsening bone resorption. Treatment with HUC-MSC secretome or NEP alone moderately diminished inflammation, however the combined therapy markedly downregulated NF-κB, IL-1β, TNF-α, and IL-6, while reinstating IL-10 and stress proteins. These modifications diminished osteoclast activation and maintained osteoblast viability, with the most significant protective impact noted in the combination group.ConclusionThe HUC-MSC secretome and NEP collaboratively influence inflammatory pathways and reinstate protective proteins in calvarial osteolysis triggered by hyperglycemia. This dual technique presents a promising acellular and natural product-based method for addressing diabetes bone loss and associated craniofacial problems. © 2026 The Authors. Published by Elsevier B.V. on behalf of Craniofacial Research Foundation. This is an open access article under the CC BY license. http://creativecommons.org/licenses/by/4.0/
Department of Biology, Faculty of Mathematic and Natural Science, Universitas Sumatera Utara, Medan, Indonesia; Department of Pharmacology, Faculty of Pharmacy, Universitas Sumatera Utara, Medan, Indonesia; Department of Orthodontic, Faculty of Dentistry, Universitas Gadjah Mada, Yogyakarta, Indonesia; Department of Biotechnology, Faculty of Mathematic and Natural Science, Universitas Negeri Malang, Malang, Indonesia; Department of Biochemistry and Molecular, Biochemistry Biomolecular Laboratory, Faculty of Medicine, Universitas Brawijaya, Surabaya, Indonesia; School of Materials and Mineral Resources Engineering, Engineering Campus, Universiti Sains Malaysia, Penang, Nibong Tebal, 14300, Malaysia; Department of Orthodontic, Faculty of Dental Medicine, Universitas Airlangga, Surabaya, Indonesia
