Streptococcus mutans GS-5 antigen I/II stimulates cell survival in serum deprived-cultures through PI3K/Akt Pathways

The antigen I/II (AgI/II) protein is a major surface protein that mediates the attachment of Streptococcus mutans (S. mutans) to the saliva‐coated pellicle. Numerous studies have investigated not only the mechanisms by which AgI/II signaling is transduced within cells, but have also attempted to use AgI/II‐specific antibodies to treat dental caries and host immune responses. However, little information is available about the effects of AgI/II on basic cellular events in bone cells. In this study, we examined the effects of the His‐tagged recombinant N‐terminal half of the AgI/II protein (rAgI/II‐N) generated from S. mutans GS‐5 on the viability, proliferation, and cell cycle progression of primary calvarial osteoblasts. We also investigated the mechanisms involved in the rAgI/II‐N‐mediated survival of serum‐starved osteoblasts. We found that rAgI/II treatment attenuated the serum deprivation‐induced decrease in cell viability and proliferation of osteoblasts. rAgI/II‐N also prevented the loss of mitochondrial membrane potential (MMP), alterations in levels of two key mitochondrial Bcl‐2 family proteins, and the accumulation of numerous cells into the sub‐G1 phase that were observed in serum‐starved osteoblasts. Pharmacological inhibitors of phosphoinositide 3‐kinase (PI3K), but not of extracellular signal‐regulated kinase or Ras, blocked the rAgI/II‐N‐mediated protection against serum deprivation‐induced cell death. Additional experiments revealed that the integrin α5β1‐mediated PI3K pathway is required for rAgI/II‐N‐mediated Akt phosphorylation in osteoblasts. Collectively, these results suggest that rAgI/II‐N induces survival signals in serum‐starved osteoblasts through integrin‐induced PI3K/Akt signaling pathways. J. Cell. Biochem. 113: 1724–1732, 2012. © 2011 Wiley Periodicals, Inc.