Differential age-related bone architecture changes between female and male STR/Ort mice.

The incidence of spontaneous osteoarthritis (OA) in female STR/Ort mice is much lower than that observed in male STR/Ort mice; however, the reason for the differential incidence of OA between sexes has not been elucidated. Here, we investigated and compared age- and sex-related bone mineral density and architectural changes in male and female STR/Ort mice. Bone architecture and bone mineral density (BMD) of femurs were examined in 5-, 10-, 15-, 20-, and 35-week-old male and female STR/Ort mice by microscopic computed tomography (µCT). Angular degrees of internal tibial torsion (ADITT) were also measured in mice at 5, 15, and 35 weeks of age. Earlier decreases of cancellous volume and BMD were found in male STR/Ort mice. Using µCT, an age-related decline of bone marrow space in femoral diaphysis was observed in both males and females but was more dramatic in females. In addition, an earlier increase of ADITT was observed in male STR/Ort mice, suggesting that internal rotation of the tibia may contribute to OA. Age- and sex-related bone architectural changes clearly differ between male and female STR/Ort mice. These differences in bone structure, particularly ADITT, may explain the differential incidence of OA in STR/Ort mice.

Basic helix-loop-helix transcription factor DEC1 negatively regulates cyclin D1.

DEC1 (also known as Stra13/Bhlhb2/Sharp2) and DEC2 (also known as Bhlhb3/Sharp1) are two paralogous basic helix-loop-helix (bHLH) transcriptional regulators which exhibit a robust circadian gene expression pattern in the suprachiasmatic nucleus (SCN) and in peripheral organs. DEC1 has been suggested to play key roles in mammalian cell differentiation, the cell cycle and circadian regulation, hypoxia response, and carcinogenesis. Here we show that DEC1 overexpression exhibits delayed wound healing and reduces cell proliferation, migration, and invasion. DEC1 strongly repressed the promoter activity of cyclin D1. We further identify a possible DEC-response element in the cyclin D1 promoter region, and confirmed the direct binding of DEC1 to that element. Forced expression of DEC1 efficiently repressed the cyclin D1 promoter and expression. Our clinical data provide the first evidence that there is a strong inverse correlation between DEC1 and cyclin D1 expression in oral cancer, and DEC1 expression significantly correlated with clinicopathological parameters. We suggest that radiation-induced DEC1 overexpression and Akt phosphorylation in cancer cells are mediated via PI-3K signalling. Overexpression of DEC1 activates the PI-3K/Akt signalling pathway through reactive oxygen species (ROS).

A novel underuse model shows that inactivity but not ovariectomy determines the deteriorated material properties and geometry of cortical bone in the tibia of adult rats.

Our goal in this study was to determine to what extent the physiologic consequences of ovariectomy (OVX) in bones are exacerbated by a lack of daily activity such as walking. We forced 14-week-old female rats to be inactive for 15 weeks with a unique experimental system that prevents standing and walking while allowing other movements. Tibiae, femora, and 4th lumbar vertebrae were analyzed by peripheral quantitative computed tomography (pQCT), microfocused X-ray computed tomography (micro-CT), histology, histomorphometry, Raman spectroscopy, and the three-point bending test. Contrary to our expectation, the exacerbation was very much limited to the cancellous bone parameters. Parameters of femur and tibia cortical bone were affected by the forced inactivity but not by OVX: (1) cross-sectional moment of inertia was significantly smaller in Sham-Inactive rat bones than that of their walking counterparts; (2) the number of sclerostin-positive osteocytes per unit cross-sectional area was larger in Sham-Inactive rat bones than in Sham-Walking rat bones; and (3) material properties such as ultimate stress of inactive rat tibia was lower than that of their walking counterparts. Of note, the additive effect of inactivity and OVX was seen only in a few parameters, such as the cancellous bone mineral density of the lumbar vertebrae and the structural parameters of cancellous bone in the lumbar vertebrae/tibiae. It is concluded that the lack of daily activity is detrimental to the strength and quality of cortical bone in the femur and tibia of rats, while lack of estrogen is not. Our inactive rat model, with the older rats, will aid the study of postmenopausal osteoporosis, the etiology of which may be both hormonal and mechanical.

Prolonged endochondral bone healing in senescence is shortened by low-intensity pulsed ultrasound in a manner dependent on COX-2.

To test whether mechanical loading produces faster healing in aged mice, fractured femurs of aged 1-year-old mice were subjected to low-intensity pulsed ultrasound (LIPUS), a treatment that is routinely used to help heal fractures in humans. Cyclooxygenase-2 knockout mice (COX-2(-/-)), which lack an immediate early mediator of mechanical stimulation, were also studied by histochemistry, microcomputed tomography and quantitative polymerase chain reaction to determine the role of COX-2. The healing in the aged COX-2(-/-) mice is slow during the endochondral bone remodeling (>30 d), a period generally prolonged in senescence. For aged wild-type mice, LIPUS halved the endochondral phase to about 10 d, whereas that was not the case for aged COX-2(-/-) mice, which showed no apparent shortening of the prolonged endochondral-phase healing time. Injecting prostaglandin E(2) receptor agonists, however, rescued the COX-2(-/-) callus from insensitivity to LIPUS. In conclusion, COX-2 is a limiting factor in the delayed endochondral bone healing and is induced by LIPUS, which normalizes healing rate to the wild-type level.

Osteoarthritic changes of the patellofemoral joint in STR/OrtCrlj mice are the earliest detectable changes and may be caused by internal tibial torsion.

STR/ort mice develop a naturally occurring osteoarthritis (OA) of the knee joints. However, the evaluation of early OA changes has been difficult due to variability caused by gender, individual differences, and differences between the right and left lower limbs. The objective of this study was to analyze the variability of the early OA changes with age in STR/ort mice and to identify the cause of onset. A total of 115 STR/OrtCrlj mice aged 10-45 weeks were examined. In addition to conventional radiological and histological evaluation of the knee joints, histological sections were used to examine the patellofemoral, femorotibial, and growth plate cartilage under similar conditions. A morphological evaluation of tibiae, including micro-3-dimensional computed tomography, was performed. Radiological evaluation showed OA changes in the joints of mice over 35 weeks old and histological evaluation showed early OA changes in the femorotibial joints of mice over 26 weeks old. However, these changes were not common in all individuals. In contrast, most common and reproducible OA changes were observed in the bilateral patellofemoral joints of all individuals, and even in subjects ranging from 10 to 20 weeks of age. Morphological evaluations also demonstrated an abnormal tibial internal torsion that increased with age and was associated with medial patellar dislocation. In conclusion, the earliest histological OA change was observed in the patellofemoral joint prior to similar observations in the femorotibial joint. Internal tibial torsion may be a cause of OA in the patellofemoral joints, which leads to the development of medial femorotibial OA.

Image quality of film transparency printer output of digital dental radiographs.

OBJECTIVE: The purpose of this study was to evaluate the physical properties of the film transparency output of a printer and its potential use in dental radiography. STUDY DESIGN: A color printer (Sony UP-D70XR) was used to produce film transparencies of digital radiographs. A physical evaluation for the image quality was conducted including measurements of the image density reproducibility, the dose response function, the root mean square (RMS) granularity and the modulation transfer function (MTF). RESULTS: The characteristic curve of the hard copy image produced a nonlinear, sigmoid response for pixel value or x-ray absorbed dose. The RMS of the scan parallel direction was greater than that of the scan perpendicular direction in low density areas, but it reversed beyond density 1.3. The MTF of the scan perpendicular direction was superior to that of the scan parallel direction. CONCLUSION: It was suggested that further examination of the image qualities of this printer is worthwhile.

Inhibitory effects of incadronate on the progression of rat experimental periodontitis by porphyromonas gingivalis infection.

BACKGROUND: Incadronate (YM175, disodium cycloheptylaminomethylenediphosphonate monohydrate), a bisphosphonate, has been suggested to prevent the bone resorption associated with periodontitis by inhibiting osteoclast activity. The purpose of this study was to investigate the effect of incadronate in preventing periodontal destruction in rats with Porphyromonas gingivalis-induced periodontitis. METHODS: Periodontitis was induced in 35 Wister rats by inoculating P. gingivalis into the oral cavity and feeding the rats a soft diet for 4 weeks. Incadronate or placebo was administered to the oral cavity of the rats 2 days per week for 2, 4, or 8 weeks. RESULTS: P. gingivalis infection resulted in destruction of the periodontal ligament, reduced bone density, and caused inflammatory cell migration. Radiographic, morphometric, and histological results showed that incadronate had the ability to increase the bone mineral density (quantum level score; cortex 518.9 [placebo 612.8]; sponge 579.8 [placebo 672.0]) and to prevent periodontal ligament destruction (width 0.16 mm [placebo 0.20 mm]; area 0.36 mm2 [placebo 0.54 mm2]) after 8 weeks' administration. Furthermore, the polymorphonuclear leukocyte (PMN) infiltration in gingival tissue was significantly decreased. CONCLUSION: These results showed that incadronate inhibits bone resorption and PMN migration in P. gingivalis-induced periodontitis.

Structuring parameters for assessment of bone quality using a morphological filter and star volume analysis: structuring property in the cancellous bone of the human femoral head.

This study examines structuring parameters for the assessment of bone quality based on the relationship of bone strength to the trabecular structure or bone mineral density (BMD). Thirty-nine human cancellous bone blocks sampled from resected Ward's triangle area were investigated. The trabecular bone pattern of each bone block was binarized into its corresponding trabecular skeletal pattern using computed radiography with a morphological filter. Every binarized trabecular skeletal pattern was quantified to find the trabecular skeletal pixel percentage (SkP = volume parameter of trabecular skeletal signal component) and skeletal star volume (Vt = connection parameter of trabecular skeletal structure). After BMD and elasticity for each bone block was measured by dual X-ray absorptiometry and the breaking test, the correlations to SkP and Vt were determined. In addition, an attempt was made to detect changes of the trabecular structure in the Ward's triangle area of the femoral head after patients had received treatment for osteoporosis. This evaluation used the structuring parameters SkP and Vt. The results showed that the larger the BMD value, the greater the elasticity, although some samples with similar BMD values had considerably different elasticities. With increased Vt values the trabecular skeletal pattern that had horizontal skeletal elements orientated perpendicular to the loading direction showed higher elasticity. No correlation between SkP and either elasticity or BMD was observed in either the subset (sequential images of morphological filter) or sumset images (combined with subset images). On the other hand, the correlation coefficient between Vt and elasticity was similar to that between BMD and elasticity for subset image ( n = 6). For sumset images (3-6 and 4-7), the correlation coefficient of Vt was equal or higher than that of BMD and the connectivity of the trabecular skeletal structure was more closely linked to bone strength as compared to BMD. Therefore, it was concluded that because no high correlation could be detected between Vt and BMD, BMD and the connectivity of trabeculae are independently related to bone strength. In addition, this method was used to evaluate patients after treatment for osteoporosis, and noticeable changes were seen in the bone trabecular skeletal structure in the Ward's triangle area of the femoral head. In reference to these clinical images, variations in SkP and Vt were quantitatively assessed. These results suggest that the SkP and Vt obtained using computed radiography, morphological filter, and star volume analysis are useful structuring parameters for the assessment of bone quality.

The application of a radiotherapy-planning system: consideration from a case of intraoral squamous cell carcinoma that lacked a control.

OBJECTIVE: The purpose of this case study was to present an applied example of a radiotherapy-planning system used during the treatment of a malignant tumor in the oral and maxillofacial region. STUDY DESIGN: The various radiotherapy modalities were performed on a patient with oral squamous cell carcinoma of multiple metachronous recurrences. Estimated radiation dose-distribution curves for each radiotherapy modality were computed by using a commercially available radiotherapy-planning system. A personal computer was used to make the superimposed radiation dose-distribution curve. RESULTS: The 3-dimensional dose-distribution curves were determined with the radiotherapy-planning system. In addition, with the use of superimposition of the dose-distribution curves from all sources of radiotherapy, it was possible to estimate regions receiving extremely high radiation dosages. This information serves as a road map to potential postradiation complication sites at follow-up examinations. CONCLUSION: The radiotherapy-planning system is very useful for the evaluation of a radiotherapy dosage to treat malignant tumors in the oral and maxillofacial region.

Assessment of bone feature parameters from lumbar trabecular skeletal patterns using mathematical morphology image processing.

In this study, bone feature parameters were obtained from digital lumbar vertebral images to determine their potential usefulness in assessing binary trabecular skeletal patterns. The system consisted of a magnification radiographic technique, computed radiography (CR), microfocused X-ray computed tomography (mu-CT), and mathematical morphology image processing. A digital CR image was produced, using a ten-times magnified lumbar vertebral cancellous bone block (1.5 x 1.5 x 1.5 cm(3)). The information was then subjected to mathematical morphology image processing, to extract eight binary trabecular skeletal patterns having different continuities as the operation number ( n) increased. These skeletal patterns were used as test patterns and analyzed quantitatively by calculation of the skeletal pixel percentage (SKP) and star volume analysis (Vsk, volume of skeletal trabecular elements; Vsp, volume of nonskeletal elements). Then the binary skeletal pattern data were converted into the mu-CT format, using a general personal computer, and the images were quantitatively analyzed with mu-CT built-in image analysis software for microstructural indices, fractal dimension analysis, and node-strut analysis. The SKP and Vsk showed an expected decrease as n increased. Concurrently, the Vsp showed an expected increase as n increased. The skeletal thickness (Sk.Th) showed a constant value at n = 1 to 4 and n = 5 to 7, but decreased in a stepwise fashion at n = 1 and n = 5. The skeletal number (Sk.N), bone area fraction (B.Ar/T.Ar) and bone perimeter fraction (B.Pm/T.Ar), decreased as n increased. Skeletal space (Sk.Sp) and perimeter-to-area ratio (B.Pm/B.Ar) increased with increasing n. In the fractal dimension analysis, the values decreased with increasing n and showed changes similar to the image observations. In fact, the SKP, star volume analysis, Sk.N, B.Ar/T.Ar, B.Pm/T.Ar, Sk.Sp, and B.Pm/B.Ar all closely mirrored the observational analysis of the images. Linkage of the skeletal structure as functions of the following parameters could be quantitatively demonstrated. The parameters used were node (Nd) and terminus (Tm). Variations in the total strut length (TSL) and Tm could demonstrate quantitative changes in skeletal structure. These results indicate that the system consisting of a combination of a magnification radiographic technique, CR, mu-CT, and mathematical morphology image processing may be a useful tool for quantitative skeletal structure analysis and the structural assessment of lumbar vertebrae, for the assessment of skeletal structural changes. It is important to choose suitable parameters for the desired structural changes.