Stretched periodontal ligament cells up-regulate Interleukin-11 to regulate osteoblastic metabolism

Objectives: The mechanical loading caused by occlusion is known to play an essential role in maintaining periodontal ligament (PDL) tissues. Interleukin-11 (IL-11) is a multi-functional cytokine involved actively in bone metabolism, and it has been reported that IL-11 induced by fluid shear stress enhanced osteoblastogenesis in murine osteoblasts. Additionally, a recent report has discussed that IL-11 would stimulate osteoblastic differentiation of PDL cells. Therefore, we hypothesized that mechanical loading may induce the expression of IL-11 in PDL tissues to regulate osteoblastic metabolism. Methods: Human PDL cells (HPDLCs) obtained from healthy molars of two patients were cultured in flexible-bottomed chambers coated with type I collagen. HPDLCs were subjected to stretch loading (0.5 sec stretch and 0.5 sec relaxation per a cycle) for 1 hr. Besides, we used a human osteoblast-like cell line, Saos-2. For gene expression analyses, semi-quantitative and quantitative RT-PCR were performed, and for protein expression analyses the enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry were performed. All procedures were approved by the Animal Research Committee of Kyushu University. Results: In the present study, we identified up-regulated gene and protein expressions of IL-11 in HPDLCs that were exposed to stretch loading. Addditionally, we also detected up-regulated gene expression of focal adhesion kinase (FAK) in HPDLCs. The inhibitor for FAK significantly inhibited gene expression of IL-11 induced by stretch loading. Immunohistochemical data revealed the intense reaction for an anti-IL-11 antibody in the bone and the cementum sides of PDL tissues. Furthermore, we found that IL-11 stimulated the proliferation and the expression of bone-related molecules in Saos-2. These data suggested that IL-11 might contribute to osteoblastic metabolism under the environment of mechanical load in PDL tissues. Conclusions: Stretch loading up-regulated the expression of IL-11 via the FAK signaling pathway in human PDL cells, and IL-11 stimulates the proliferation and the differentiation of osteoblasts.