Submandibular saliva from male rats modulates osteogenic differentiation of bone marrow progenitor cells In Vitro.

OBJECTIVE: To investigate the effect of submandibular saliva from male rats on the proliferation and osteoblastic differentiation of bone marrow progenitor cells.

DESIGN: Saliva was collected and pooled from adult male rats, and the total protein content was measured. Bone marrow progenitor cells (BMPC) from adult male rats were incubated with varying concentrations of salivary protein (ranging from 0 to 30 µg/mL) to assess cell proliferation. Osteoblastic differentiation was evaluated by measuring alkaline phosphatase activity, collagen type 1 production, mineral nodule formation, and molecular markers of differentiation after 7, 15, or 21 days of saliva exposure in a differentiating culture medium. The pro-inflammatory effects of saliva on BMPC were assessed by measuring tumor necrosis factor-alpha, interleukin 1 beta, prostaglandin E2, and matrix metalloproteinases 2 and 9.

RESULTS: Low saliva concentration stimulated BMPC, promoting a pro-secretory and proliferative state. In contrast, higher concentration inhibited both processes under basal conditions. Furthermore, in osteogenic medium, saliva decreased alkaline phosphatase activity, collagen-1 production, and matrix mineralization in BMPC, demonstrating a dose- and time-dependent effect. Saliva also increased the secretion of interleukin 1β, tumor necrosis factor α, prostaglandin E2, and metalloproteinase activity in these cells, which inhibited osteoblastic differentiation.

CONCLUSION: Submandibular saliva has a biphasic effect on the osteogenic commitment of bone marrow progenitor cells, depending on the concentration and duration of exposure. This finding underscores the active role of saliva in the repair and regeneration of tooth sockets.