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

Nugraha AP 1 , Yang K 2 , Pramusita A 1 , Putranti NAR 1 , Luthfi M 3 , Ramadhani NF 4 Show all authors , Sitalaksmi RM 5 , Situmorang PC 6 , Artasasta MA 7 , Alhasyimi AA 8 , Riawan W 9 , Nugraha AP 10 , Shariff KA 11 , Tanimoto K 12 , Hong G 2

Affiliations 

  • 1 Dental Regenerative Research Group, Department of Orthodontics, Faculty of Dental Medicine, Universitas Airlangga, Surabaya, Indonesia
  • 2 Division for Globalization Initiative, Liaison Center for Innovative Dentistry, Graduate School of Dentistry, Tohoku University, Sendai, Japan
  • 3 Department of Oral Biology, Faculty of Dental Medicine, Universitas Airlangga, Surabaya, Indonesia
  • 4 Department of Dentomaxillofacial Radiology, Faculty of Dental Medicine, Universitas Airlangga, Surabaya, Indonesia
  • 5 Department of Prosthodontics, Faculty of Dental Medicine, Universitas Airlangga, Surabaya, Indonesia
  • 6 Biology Study Program, Faculty of Mathematics and Natural Sciences, Universitas Sumatera Utara, Medan, Indonesia
  • 7 Biotechnology Program, Departement of Applied Science, Faculty of Mathematics and Natural Science, Universitas Negeri Malang, Malang, Indonesia
  • 8 Department of Orthodontics, Faculty of Dentistry, Universitas Gadjah Mada, Special Region of Yogyakarta, Indonesia
  • 9 Department of Biomolecular Biochemistry, Faculty of Medicine, Universitas Brawijaya, Malang, Indonesia
  • 10 Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia
  • 11 School of Materials and Mineral Resources Engineering, Engineering Campus, Universiti Sains Malaysia, Penang, Malaysia
  • 12 Department of Orthodontics and Craniofacial Developmental Biology, Hiroshima University Graduate Schoolof Biomedical and Health Sciences, Hiroshima, Japan
J Dent Sci, 2025 Oct;20(4):2181-2188.
PMID: 41040564 DOI: 10.1016/j.jds.2025.07.003

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.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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