A central role for the nuclear factor-kappaB pathway in anti-inflammatory and proinflammatory actions of mechanical strain.

Mechanical signals play an integral role in bone homeostasis. These signals are observed at the interface of bone and teeth, where osteoblast-like periodontal ligament (PDL) cells constantly take part in bone formation and resorption in response to applied mechanical forces. Earlier, we reported that signals generated by tensile strain of low magnitude (TENS-L) are antiinflammatory, whereas tensile strain of high magnitude (TENS-H) is proinflammatory and catabolic. In this study, we examined the mechanisms of intracellular actions of the antiinflammatory and proinflammatory signals generated by TENS of various magnitudes. We show that both low and high magnitudes of mechanical strain exploit nuclear factor (NF)-kappaB as a common pathway for transcriptional inhibition/activation of proinflammatory genes and catabolic processes. TENS-L is a potent inhibitor of interleukin (IL)-1 beta-induced I-kappaBbeta degradation and prevents dissociation of NF-kB from cytoplasmic complexes and thus its nuclear translocation. This leads to sustained suppression of IL-1beta-induced NF-kappaB transcriptional regulation of proinflammatory genes. In contrast, TENS-H is a proinflammatory signal that induces I-kappaBbeta degradation, nuclear translocation of NF-kappaB, and transcriptional activation of proinflammatory genes. These findings are the first to describe the largely unknown intracellular mechanism of action of applied tensile forces in osteoblast-like cells and have critical implications in bone remodeling.