Propolis nanoemulsion and mesenchymal stem cell conditioned medium promote osteoblastogenesis against lipopolysaccharide-induced osteolysis in hyperglycemic rats.

Hyperglycemia is known to worsen lipopolysaccharide (LPS)-induced inflammatory osteolysis. However, regenerative therapy with human umbilical cord mesenchymal stem cells conditioned medium (HUCMSCs-CM) and Tetragonula biroi propolis nanoemulsion (PNE) may suppress inflammatory osteolysis with hyperglycemia. This study investigated how HUCMSCs-CM and PNE affected the osteoblastogenesis markers in rats with hyperglycemia and inflammatory osteolysis. Twenty-eight healthy male rats (1–2 months old) were divided into seven groups: NC (negative control), LP (100 µL LPS), HG (> 230 mg/dL), LH (100 µL LPS with hyperglycemia), LHH (LPS, hyperglycemia, and 100 µL HUCMSCs-CM), LHN (LPS, hyperglycemia, and 100 µL PNE), and LHHN (LPS, hyperglycemia), and 100 µL LPS from Escherichia coli was used to induce calvarial osteolysis. PNE and HUCMSCs-CM were prepared and administered subcutaneously into the calvaria. Thereafter, hyperglycemia was induced via intraperitoneal administration of 30 mg/kg of streptozotocin for 1 week. The rats were sacrificed on day 8, and ELISA was used to measure Coll1a1, ALP, and osteopontin in the blood samples. Immunohistochemistry was employed to examine the osteoblastogenesis markers; RUNX-2, osterix, osteonectin, and osteocalcin. In the LPS-induced inflammatory osteolysis model with hyperglycemia, administration of HUCMSCs and PNE significantly increased osteoblastogenesis markers (P ≤ 0.05). The combination treatment showed the most pronounced effect, enhancing serum Coll1a1, ALP, and osteopontin levels, as well as RUNX-2, osterix, osteonectin, and osteocalcin expression. These findings indicate that HUCMSCs-CM and PNE synergistically promote osteoblastogenesis in hyperglycemia-aggravated inflammatory osteolysis and may represent a promising regenerative therapeutic strategy for inflammatory bone loss under compromised metabolic conditions.