Abstract
ObjectivesOrthodontic treatment in adult patients predisposed to mild or severe periodontal disease is challenging for orthodontists. Orthodontic malpractice or hyper-occlusal forces may aggravate periodontitis-induced destruction of periodontal tissues, but the specific mechanism remains unknown. In the present study, the combined effect of mechanical stress and tumor necrosis factor (TNF)-α on the inflammatory response in human periodontal ligament stromal cells (hPDLSCs) was investigated.Materials and methodshPDLSCs from 5 healthy donors were treated with TNF-α and/or subjected to cyclic tensile strain (CTS) of 6% or 12% elongation with 0.1 Hz for 6- and 24 h. The gene expression of interleukin (IL)-6, IL-8 and cell adhesion molecules VCAM and ICAM was analyzed by qPCR. The protein levels of IL-6 and IL-8 in conditioned media was measured by ELISA. The surface expression of VCAM-1 and ICAM-1 was quantified by immunostaining followed by flow cytometry analysis.ResultsTNF-α-induced IL-6 gene and protein expression was inhibited by CTS, whereas TNF-α-induced IL-8 expression was decreased at mRNA expression level but enhanced at the protein level in a magnitude-dependent manner. CTS downregulated the gene expression of VCAM-1 and ICAM-1 under TNF-α stimulation, but the downregulation of the surface expression analyzed by flow cytometry was observed chiefly for VCAM-1.ConclusionsOur findings show that mechanical force differentially regulates TNF-α-induced expression of inflammatory mediators and adhesion molecules at the early stage of force application. The effect of cyclic tensile strain is complex and could be either anti-inflammatory or pro-inflammatory depending on the type of pro-inflammatory mediators and force magnitude.Clinical relevanceOrthodontic forces regulate the inflammatory mediators of periodontitis. The underlying mechanism may have significant implications for future strategies of combined periodontal and orthodontic treatment.
Highlights
Periodontal ligament (PDL) is a connective tissue between the cementum and the alveolar bone, which supports the teeth and is continuously subjected to and responding to varied types of biomechanical forces [1, 2]
tumor necrosis factor (TNF)-α induced the protein production of both IL-6 and IL-8, which was significantly increased in a time-dependent manner (Figs. 2c and 2d)
The different effects may be attributed to the differences between application of physiological and pathological stretch [72]. This in vitro study demonstrated that application of cyclic tensile strain (CTS) with 6% or 12% elongation decreased the TNF-a induced gene and protein expression of IL-6, vascular cell adhesion molecule 1 (VCAM-1) and intercellular adhesion molecule 1 (ICAM-1)
Summary
Periodontal ligament (PDL) is a connective tissue between the cementum and the alveolar bone, which supports the teeth and is continuously subjected to and responding to varied types of biomechanical forces [1, 2]. Appropriate mechanical force squeezes or stretches the PDL, regulating a coordinated remodeling process which consists of bone resorption at compression side and bone formation at tension side of the alveolar bone, and culminating in the orthodontic tooth movement (OTM) [3]. This process highly depends on the cellular components of PDL, which principally consist of undifferentiated. ICAM-1 and VCAM-1 mediate the immunomodulatory function of MSCs [22]
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