Human umbilical cord mesenchymal stem cells secretome and nanoemulsion propolis combination ameliorate osteoclastogenesis in lipopolysaccharide-induced osteolysis in hyperglycemia rats

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Alexander Patera Nugraha, Kunhua Yang, Adya Pramusita, Nurul Aisyah Rizky Putranti, Muhammad Luthfi, Nastiti Faradilla Ramadhani, Ratri Maya Sitalaksmi, Putri Cahaya Situmorang, Muh. Ade Artasasta, Ananto Ali Alhasyimi, Wibi Riawan, Albertus Putera Nugraha, Khairul Anuar Shariff, Kotaro Tanimoto, Guang Hong

2025 Journal of Dental Sciences Vol. 20 Issue 4 Article Cited by 2 Quartile

Abstract

Background/purpose: Human umbilical cord mesenchymal stem cell secretome (HUCMSCS) and nanoemulsion propolis (NEP) from Tetragonula biroi may be beneficial regenerative medicine to reduce LPS-induced osteolysis with hyperglycemia. This study aimed to investigate the HUCMSCS and NEP effect on nuclear factor associated T-cell-1 (NFATc1), sclerostin, receptor activator kappa beta (RANK), its ligand (RANKL), the osteoprotegerin (OPG) expression, tartrate-resistant acid phosphatase (TRAPase), and cathepsin K (Ctsk) serum level in LPS-induced osteolysis in hyperglycemic Wistar rats (Rattus novergicus). Materials and methods: Twenty-eight healthy male Wistar rats, 1–2 months old and 250–300 g body weight, were divided into seven groups, namely K1: control group; K2: 100 μl LPS; K3: hyperglycemia (≥230 mg/dL); K4: 100 μl LPS with hyperglycemia; K5: LPS, hyperglycemia, and 100 μl NEP; K6: LPS, hyperglycemia, and 100 μl HUCMSCS; and K7: LPS, hyperglycemia, and 100 μl HUCMSCS and NEP. Escherichia coli`s LPS was used to induce osteolysis on the calvaria. NEP and HUCMSCS were formulated and collected, then injected subcutaneously on the calvaria. Hyperglycemia-induced streptozotocin 30 mg/kg injection for one week, intraperitoneally. All samples were sacrificed on day 8. Blood samples were collected to examine TRAP and Ctsk levels with enzyme-linked immunosorbent assay. NFATc1, sclerostin, and RANK-RANKL-OPG expression investigated with immunohistochemistry. Results: HUCMSCS and NEP administration inhibit TRAP and Ctsk levels, reduce NFATc1, sclerostin, and RANK-RANKL, but enhance OPG expression in LPS-induced osteolysis with hyperglycemia with significant differences between groups (P ≤ 0.05). Conclusion: HUCMSCS and NEP post-administration reduced osteoclastogenesis in LPS-induced osteolysis calvaria with hyperglycemic in rats in the early phase of bone remodelling. © 2025 Association for Dental Sciences of the Republic of China

Affiliations

Dental Regenerative Research Group, Department of Orthodontics, Faculty of Dental Medicine, Universitas Airlangga, Surabaya, Indonesia; Division for Globalization Initiative, Liaison Center for Innovative Dentistry, of Dentistry, Tohoku University, Sendai, Japan; Department of Oral Biology, Faculty of Dental Medicine, Universitas Airlangga, Surabaya, Indonesia; Department of Dentomaxillofacial Radiology, Faculty of Dental Medicine, Universitas Airlangga, Surabaya, Indonesia; Department of Prosthodontics, Faculty of Dental Medicine, Universitas Airlangga, Surabaya, Indonesia; Biology Study Program, Faculty of Mathematics and Natural Sciences, Universitas Sumatera Utara, Medan, Indonesia; Biotechnology Program, Departement of Applied Science, Faculty of Mathematics and Natural Science, Universitas Negeri Malang, Malang, Indonesia; Department of Orthodontics, Faculty of Dentistry, Universitas Gadjah Mada, Special Region of Yogyakarta, Indonesia; Department of Biomolecular Biochemistry, Faculty of Medicine, Universitas Brawijaya, Malang, Indonesia; Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia; School of Materials and Mineral Resources Engineering, Engineering Campus, Universiti Sains Malaysia, Penang, Malaysia; Department of Orthodontics and Craniofacial Developmental Biology, Hiroshima University Graduate Schoolof Biomedical and Health Sciences, Hiroshima, Japan