Human Periodontal Ligament Fibroblasts Stimulate Osteoclastogenesis in Response to Compression Force Through TNF-α-Mediated Activation of CD4+T Cells

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-kappa B) ligand (RANKL). In particular, PLF increased the expression of tumor necrosis factor (TNF)-alpha 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-alpha 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-alpha or TNF receptor. Collectively, the current findings suggest that PLF secrete relatively higher levels of TNF-alpha 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. J. Cell. Biochem. 112: 2891-2901, 2011. (C) 2011 Wiley-Liss, Inc.