In vivo effects of zoledronic acid on oral mucosal epithelial cells.

OBJECTIVE: Osteonecrosis of the jaw is a serious complication of bisphosphonate treatment for which the pathophysiology is unknown. The purpose of this study was to investigate whether in vivo zoledronic acid (ZA) induces alterations in cell proliferation, apoptosis, and matrix metalloproteinases (MMPs) expression in oral mucosal epithelial cells. METHODS: One-year-old dogs were either untreated (control group) or given high doses of intravenous ZA (ZA group) for 3 months. The doses of ZA were equivalent to those given to cancer patients, yet were administered two times more frequently (every 2 weeks). Mucosal tissues were assessed immunohistochemically for cell proliferation (proliferating cell nuclear antigen, PCNA), matrix metalloproteinase (MMP) expression, and apoptosis (caspase 3 and TUNEL). RESULTS: There were no significant differences between the groups with respect to PCNA, MMP-2, MMP-14, and TUNEL positive cells. However, the expression of MMP-9 was significantly higher in the control group than in the ZA group (P < 0.05), whereas the expression of caspase 3 was significantly lower in the control group than in the ZA group (P < 0.05). CONCLUSION: These results suggest that high doses of ZA resulted in higher levels of apoptosis and lower levels of MMP-9 in the oral epithelial cells supporting the idea of bisphosphonate treatment affects the oral mucosa.

Biodegradation of a dental resin material by fibroblast conditioned media.

OBJECTIVE: Hydrolytic activity is increased in conditioned media from human gingival and pulp fibroblasts in response to exposure to triethyleneglycol dimethacrylate (TEGDMA). The purpose of this study was to determine if this conditioned media with hydrolytic activity could cause the biodegradation of a dental resin material. METHODS: Resin material specimens were stored for 30 days at 37 degrees C in distilled water, unconditioned media, artificial serum, conditioned media from human gingival and pulp fibroblasts and conditioned media from human pulp and gingival fibroblasts that were exposed to TEGDMA. The media was exchanged every other day. The specimens were subjected to Fourier transform infrared spectroscopy (FTIR) before and after storage. The area under the carbonyl peak was calculated for all the specimens to determine the extent of the degradation. RESULTS: Differences before and after storage in the area under the carbonyl peak were statistically significant for the specimens stored in the conditioned media from the fibroblasts that were exposed to TEGDMA. All of the other specimens did not produce differences in the area under the carbonyl peak that were statistically significant when comparing the before and after storage results. SIGNIFICANCE: The biodegradation demonstrated here could contribute to the marginal leaking seen clinically with the use of resin materials in dental restorations.

In vitro induction of hydrolytic activity in human gingival and pulp fibroblasts by triethylene glycol dimethacrylate and monocyte chemotatic protein-1.

OBJECTIVE: Some dental resin composite materials leach the monomer triethylene glycol dimethacrylate (TEGDMA), which could contribute to the inflammatory reaction. The purpose of this study was to examine the ability of TEGDMA to alter cytokine/growth factor secretion and enzymatic activity in monocyte derived macrophages (U937 cells), human gingival fibroblasts (HGFs), and human pulp fibroblasts (DPFs). METHODS: A human growth factor/cytokine antibody array was utilized to determine whether TEGDMA alters the expression of cytokines/growth factors from U937 cells, HGFs, and DPFs. To determine if TEGDMA alters the hydrolase activity of U937, DPF, and HGF cells, the hydrolysis of p-nitrophenyl butyrate was utilized in a spectrophotometric assay. RESULTS: TEGDMA exposure induced the expression of monocyte chemotatic protein-1 (MCP-1) from the U937 cells. Both the cell lysates and conditioned media from the HGFs showed increased hydrolase activity after exposure to a sublethal concentration of TEGDMA. MCP-1 alone increased the hydrolytic activity and the combination of MCP-1 and TEGDMA was additive in HGF conditioned media. The DPFs were also exposed to MCP-1 alone and followed by a sublethal concentration of TEGDMA. The effect of MCP-1 was greater than that of TEGDMA. SIGNIFICANCE: These results demonstrate that TEGDMA induces enzymatic activity and cytokine/growth factor expression in a cell-specific manner.