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.

The aim of this study was to evaluate osseous healing in mandibular defects using fractal analyses on conventional radiographs and tuned aperture computed tomography (TACT; OrthoTACT, Instrumentarium Imaging, Helsinki, Finland) images. Eighty test sites on the inferior margins of rabbit mandibles were subject to lesion induction and treated with one of the following: no treatment (controls); osteoblasts only; polymer matrix only; or osteoblast-polymer matrix (OPM) combination. Images were acquired using conventional radiography and TACT, including unprocessed TACT (TACT-U) and iteratively restored TACT (TACT-IR). Healing was followed up over time and images acquired at 3, 6, 9, and 12 weeks post-surgery. Fractal dimension (FD) was computed within regions of interest in the defects using the TACT workbench. Results were analyzed for effects produced by imaging modality, treatment modality, time after surgery and lesion location. Histomorphometric data were available to assess ground truth. Significant differences (p < 0.0001) were noted based on imaging modality with TACT-IR recording the highest mean fractal dimension (MFD), followed by TACT-U and conventional images, in that order. Sites treated with OPM recorded the highest MFDs among all treatment modalities (p < 0.0001). The highest MFD based on time was recorded at 3 weeks and differed significantly with 12 weeks (p < 0.035). Correlation of FD with results of histomorphometric data was high (r = 0.79; p < 0.001). The FD computed on TACT-IR showed the highest correlation with histomorphometric data, thus establishing the fact TACT is a more efficient and accurate imaging modality for quantification of osseous changes within healing bony defects.

Quantification of osseous healing is a challenging task, requiring expensive advanced imaging modalities. To improve diagnostic osseous imaging, we undertook this prospective study to explore the potential of Tuned Aperture Computed Tomography. Eighty defects in 20 rabbit mandibles, randomly carrying an osteoblast suspension or a polymer matrix or a combination thereof or no treatment, were imaged at 3, 6, 9, and 12 weeks post-surgery. TACT slices, iteratively restored TACT, and conventional digital radiographs were evaluated. Mean-gray-value distribution within regions of interest was correlated with histomorphometric data. Lesions treated with osteoblast/polymer-matrix delivery systems demonstrated the highest mean gray-value, while the diagnostic efficacy of TACT-IR was significantly better than that of other imaging modalities (p < 0.001). Thus, TACT is an accurate imaging modality for non-destructive quantification of osseous dynamics.

Potential for TACT to accurately detect osseous healing in surgical defects was demonstrated. High resolution of TACT combined with generation of information in 3D yields comparable performance to CT.

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