Mineral trioxide aggregate (MTA) inhibits osteoclastogenesis and osteoclast activation through calcium and aluminum activities

ObjectiveTo evaluate the effect(s) of mineral trioxide aggregate (MTA) on in vitro RANKL-mediated osteoclast-dependent bone resorption events and the influence of Ca2+ and Al3+ on the osteoclastogenesis inhibition by MTA.Materials and methodsTwo types of osteoclast precursors, RAW 264.7 (RAW) cell line or bone marrow cells (obtained from BALB/c mice and stimulated with recombinant (r) macrophage colony stimulation factor (M-CSF), were stimulated with or without recombinant (r) activator of nuclear kappa B ligand (RANKL), in the presence or absence of MTA for 6 to 8 days. White Angelus MTA and Bios MTA (Angelus, Londrina, Parana, Brazil) were prepared and inserted into capillary tubes (direct contact surface=0.50 mm(2) and 0.01 mm(2)). Influence of MTA on these types of osteoclast precursors was measured by the number of differentiated tartrate-resistant acid phosphatase (TRAP)-positive multinuclear cells (RAW and bone marrow cells), TRAP enzyme activity (RAW cells), cathepsin K gene expression (RAW cells), and resorptive pit formation (RAW cells) by mature osteoclasts. Besides, RAW cells were also stimulated with Ca2+ and Al3+ to evaluate the influence of these ions on MTA anti-osteoclastogenic potential.ResultsIn bone marrow and RAW cells, the number of TRAP-positive mature osteoclast cells induced by rRANKL was significantly inhibited by the presence of MTA compared with control rRANKL stimulation without MTA (p<0.05), along with the reduction of TRAP enzyme activity (p<0.05) and the low expression of cathepsin K gene (p<0.05). In contrast, to control mature osteoclasts, the resorption area on dentin was significantly decreased for mature osteoclasts incubated with MTA (p<0.05). rRANKL-stimulated RAW cells treated with Ca2+ and Al3+ decreased the number of osteoclasts cells. Besides, the aluminum oxide was the dominant suppressor of the osteoclastogenesis process.ConclusionsMTA significantly suppressed RANKL-mediated osteoclastogenesis and osteoclast activity and, therefore, appears able to suppress bone resorption events in periapical lesions. This process might be related to Ca2+ and Al3+ activities.Clinical relevanceMTA is an important worldwidely acknowleged biomaterial. The knowledge about its molecular activities on osteoclasts might contribute to improving the understanding of its clinical efficacy.

Automated summary

The study evaluated the effect of MTA on in vitro bone resorption events mediated by RANKL and the influence of Ca2+ and Al3+ on osteoclastogenesis inhibition by MTA. Results showed that MTA significantly suppressed osteoclastogenesis and activity induced by RANKL, suggesting its potential to inhibit bone resorption events in periapical lesions. Additionally, Ca2+ and Al3+ were found to play a role in this process.