Interleukin-1 beta Induced Matrix Metalloproteinase Expression in Human Periodontal Ligament-Derived Mesenchymal Stromal Cells under In Vitro Simulated Static Orthodontic Forces

The periodontal ligament (PDL) responds to applied orthodontic forces by extracellular matrix (ECM) remodeling, in which human periodontal ligament-derived mesenchymal stromal cells (hPDL-MSCs) are largely involved by producing matrix metalloproteinases (MMPs) and their local inhibitors (TIMPs). Apart from orthodontic forces, the synthesis of MMPs and TIMPs is influenced by the aseptic inflammation occurring during orthodontic treatment. Interleukin (IL)-1 beta is one of the most abundant inflammatory mediators in this process and crucially affects the expression of MMPs and TIMPs in the presence of cyclic low-magnitude orthodontic tensile forces. In this study we aimed to investigate, for the first time, how IL-1 beta induced expression of MMPs, TIMPs and how IL-1 beta in hPDL-MSCs was changed after applying in vitro low-magnitude orthodontic tensile strains in a static application mode. Hence, primary hPDL-MSCs were stimulated with IL-1 beta in combination with static tensile strains (STS) with 6% elongation. After 6- and 24 h, MMP-1, MMP-2, TIMP-1 and IL-1 beta expression levels were measured. STS alone had no influence on the basal expression of investigated target genes, whereas IL-1 beta caused increased expression of these genes. In combination, they increased the gene and protein expression of MMP-1 and the gene expression of MMP-2 after 24 h. After 6 h, STS reduced IL-1 beta-induced MMP-1 synthesis and MMP-2 gene expression. IL-1 beta-induced TIMP-1 gene expression was decreased by STS after 6- and 24-h. At both time points, the IL-1 beta-induced gene expression of IL-1 beta was increased. Additionally, this study showed that fetal bovine serum (FBS) caused an overall suppression of IL-1 beta-induced expression of MMP-1, MMP-2 and TIMP-1. Further, it caused lower or opposite effects of STS on IL-1 beta-induced expression. These observations suggest that low-magnitude orthodontic tensile strains may favor a more inflammatory and destructive response of hPDL-MSCs when using a static application form and that this response is highly influenced by the presence of FBS in vitro.

Automated summary

The periodontal ligament responds to orthodontic forces by ECM remodeling, influenced by IL-1 beta and aseptic inflammation. IL-1 beta affects the expression of MMPs and TIMPs in hPDL-MSCs under low-magnitude orthodontic forces. FBS suppresses IL-1 beta-induced expression of MMPs and TIMPs, suggesting a complex interplay in the response of hPDL-MSCs to static orthodontic strains.