Deconvoluting the mechanisms of crestal bone loss around dental implants

Objectives: The purpose of this work was to investigate the possible mechanisms leading to crestal bone loss around dental implants. Crestal bone loss is observed radiographically around dental implants within the first five years of function. Although the mechanism for this bone loss has not been elucidated, the microgap, the space between an implant and its abutment, has been implicated as it may harbor bacteria. We hypothesized that bacterial products originating from the microgap cause the upregulation of cytokines in otherwise healthy peri-implant stromal cells and/or macrophages, which could result in osteoclast formation and, ultimately, in bone resorption. Methods: Mouse macrophage (MMΦ), rat stromal bone marrow cells (RSBM) and human gingival fibroblasts (HGF) were stimulated with lipopolysaccaride (LPS) and compared to unstimulated controls. These cells were seeded into 6 well plates and, after confluence, 1µg/ml LPS was added to the culture medium every 24 hrs for 24, 48, 96hrs. mRNA was isolated from cells and expression of IL-1α, IL-1β, and TNF-α was analyzed by RT-PCR. Results: In cell cultures of MMΦ, RSBM and HGF, mRNAs of IL-1α and IL-1β were expressed under LPS stimulation, but were not observed in cultures without LPS stimulation. TNF-α was expressed in RSBM cultures in the presence of LPS but not expressed in HGF cultures with/without LPS. In MMΦ cultures, mRNA of TNF- α was expressed in the presence and absence of LPS. Conclusion: We have demonstrated that LPS stimulates IL-1α and IL-1β expression in MMΦ, RSBM and HGF, which represent cell types present in the peri-implant connective tissue. IL-1α and IL-1β have the capacity to induce the differentiation and activation of osteoclasts resulting in bone resorption.