Calcitriol suppresses lipopolysaccharide-induced alveolar bone damage in rats by regulating T helper cell subset polarization.

BACKGROUND

Although the immunomodulatory properties of calcitriol in bone metabolism have been documented for decades, its therapeutic role in the management of periodontitis remains largely unexplored. In this study, we hypothesized that calcitriol suppresses lipopolysaccharide (LPS)-induced alveolar bone loss by regulating T helper (Th) cell subset polarization.

METHODS

To test this hypothesis, we determined the effect of calcitriol intervention on the development of LPS-induced periodontitis in rats in terms of bone loss (micro-CT analysis), local inflammatory infiltration levels, the number of osteoclasts (hematoxylin and eosin staining) and the level of osteoclastogenesis (tartrate-resistant acid phosphatase method). Furthermore, immunohistochemistry was used to assess the expression levels of the receptor activator of NF-κB ligand (RANKL) and osteoprotegerin (OPG) as well as the cytokine levels of interferon-γ (IFN-γ), interleukin-4 (IL-4), IL-17, and IL-10 throughout the LPS-injected region. Finally, the polarization potential of Th cells in peripheral blood was analyzed using flow cytometry.

RESULTS

Calcitriol intervention decreased alveolar bone loss in response to LPS injection and inflammatory cell infiltration. Analysis of osteoclast number and RANKL and OPG expression showed that bone resorption activity was largely suppressed in response to calcitriol administration, along with decreased IL-17 levels but increased IL-4 and IL-10 levels in periodontal tissues (the LPS-injected region). Similarly, the percentages of Th2 and Treg cells in peripheral blood increased, but the percentages of Th1 and Th17 cells decreased in rats receiving calcitriol.

CONCLUSION

Our findings suggest that calcitriol can be used to inhibit bone loss in experimental periodontitis, likely via the regulation of local and systemic Th cell polarization.