Human periodontal ligament fibroblasts stimulate osteoclastogenesis in response to compression force through TNF-α-mediated activation of CD4+ T cells

Abstract

Periodontal ligament fibroblasts (PLF) sense and respond to mechanical stimuli and participate in alveolar bone resorption during orthodontic treatments. This study examined how PLF influence osteoclastogenesis from bone marrow-derived macrophages (BMM) after application of tension or compression force. We also investigated whether lymphocytes could be a primary stimulator of osteoclastic activation during alveolar bone remodeling. We found that mechanical forces inhibited osteoclastic differentiation from BMM in co-cultures with PLF, with PLF producing predominantly osteoprotegerin (OPG) rather than receptor activator of nuclear factor-kappaB (NF-κB) ligand (RANKL). In particular, PLF increased the expression of tumor necrosis factor (TNF)-α in response to compression. Additional experiments showed the presence of CD4- and B220-positive cells with a subsequent increase in tartrate-resistant acid phosphatase (TRAP)-positive cells and RANKL expression only at the compression side of the force-subjected periodontal tissues. Exogenous TNF-α increased the number of TRAP-positive cells and pit formation in the co-cultures of BMM with Jurkat, but not with BJAB cells and this effect was almost completely inhibited by antibodies to TNF-α or TNF receptor. Collectively, the current findings suggest that PLF secrete relatively higher levels of TNF-α at the compression side than at the tension side and this imbalance leads to RANKL expression by activating CD4+ T cells, thereby facilitating bone resorption during orthodontic tooth movement.

Mechanical Forces Exacerbate Periodontal Defects in Bsp-null Mice

“…Alveolar bone resorption can result from excessive compression forces or occlusal stress by stimulation of osteoclastogenesis through local upregulation of RANKL, such as directed resorption on the compression side during orthodontic tooth movement (Walker et al 2008;Wise and King 2008;Sanuki et al 2010;Kook et al 2011 Based on micro-computed tomography, incisor dentin thickness, area, and mineral density were analyzed at (1) alveolar crest, (2) mental foramen, (3) first molar, and (4) third molar. Linear measurements were also performed to determine thickness of incisor enamel, labial and lingual dentin, as well as cross-sectional area of the dentin and enamel.…”

Evaluation of Oxidative Stress Biomarkers in Patients with Fixed Orthodontic Appliances

“…In the studies, cytokines have been reported to reflect the local microenvironmental status of periodontal tissues affected by orthodontic forces and to play a key role in the process of bone remodeling that is generated by orthodontic forces [3–6]. …”

Cyclic Tensile Stress During Physiological Occlusal Force Enhances Osteogenic Differentiation of Human Periodontal Ligament Cells via ERK1/2-Elk1 MAPK Pathway

“…Kook and Lee (2012) demonstrated that 1.5% elongation tension-stimulated expression of COL I and MMP-1 was controlled by the ERK/JNK-AP-1 and ERK-NF-kB signaling pathways and inhibited the proliferation of human PDL fibroblasts through Ras-p38 MAPK up-regulation. Human PDL fibroblasts stimulate osteoclastogenesis in response to compression force through TNF-alpha-mediated activation of CD4 + T cells (Kook et al, 2011b). Osteopontin expression in mechanical force-subjected PDL fibroblasts was activated by the ERK pathway (Hong et al, 2010).…”