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Dose-dependent effects of genistein on bone homeostasis in rats' mandibular subchondral bone.

ABSTRACT: AIM: To investigate the effect of genistein on bone homeostasis in mandibular subchondral bone of rats. METHODS: Female SD rats were administered with genistein (10 and 50 mg/kg) or placebo by oral gavage for 6 weeks. Then the animals were sacrificed, and histomorphology and micro-structure of mandibular condyle were examined using HE staining and micro-CT analysis, respectively. The expression levels of alkaline phosphatase (ALP), osteocalcin (OC), osteoprotegerin (OPG), the receptor activator of nuclear factor ?B ligand (RANKL) and estrogen receptors (ERs) in mandibular condyle were detected using real-time PCR. Cultured osteoblasts were prepared from rat mandibular condyle for in in vitro study. The cells were treated with genistein (10(-7) or 10(-4) mol/L) for 48 h. The expression of the bone homeostasis-associated factors and estrogen receptors (ERs) was detected using real-time PCR, and ER silencing was performed. RESULTS: At both the low- and high-doses, genistein significantly increased the bone mineral density (BMD) and bone volume, and resulted in thicker subchondral trabecular bone in vivo. In both in vivo and in vitro study, the low-dose genistein significantly increased the expression of ALP, OC and OPG, but decreased the expression of RANKL and the RANKL/OPG ratio. The high-dose genistein decreased the expression of all these bone homeostasis-associated factors. Both the low and high doses of genistein significantly increased the expression of ER?, while ER? expression was increased by the low dose genistein and decreased by the high dose genistein. ER? silencing abrogated most of the effects of genistein treatment. CONCLUSION: In rat mandibular condylar subchondral bone, low-dose genistein increases bone formation and inhibit bone resorption, while excess genistein inhibits both bone formation and resorption. The effects of genistein were predominantly mediated through ER?.

SUBMITTER: Li YQ

PROVIDER: S-EPMC4010271 | biostudies-literature | 2012 Jan

REPOSITORIES: biostudies-literature

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Dose-dependent effects of genistein on bone homeostasis in rats' mandibular subchondral bone.

Li Yong-qi YQ Xing Xiang-hui XH Wang Hui H Weng Xi-li XL Yu Shi-bin SB Dong Guang-ying GY

Acta pharmacologica Sinica 20111128 1

<h4>Aim</h4>To investigate the effect of genistein on bone homeostasis in mandibular subchondral bone of rats.<h4>Methods</h4>Female SD rats were administered with genistein (10 and 50 mg/kg) or placebo by oral gavage for 6 weeks. Then the animals were sacrificed, and histomorphology and micro-structure of mandibular condyle were examined using HE staining and micro-CT analysis, respectively. The expression levels of alkaline phosphatase (ALP), osteocalcin (OC), osteoprotegerin (OPG), the recept ...[more]

PMID: 22120966

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Project description:BackgroundSubchondral bone cysts are a widely observed, but poorly understood, feature in patients with knee osteoarthritis (OA). Clinical quantitative computed tomography (QCT) has the potential to characterize cysts in vivo but it is unclear which specific cyst parameters (e.g., number, size) are associated with clinical signs of OA, such as disease severity or pain. The objective of this study was to use QCT-based image-processing techniques to characterize subchondral tibial cysts in patients with knee OA and to explore relationships between proximal tibial subchondral cyst parameters and subchondral bone density as well as clinical characteristics of OA (alignment, joint space narrowing (JSN), OA severity, pain) in patients with knee OA.MethodsThe preoperative knee of 42 knee arthroplasty patients was scanned using QCT. Patient characteristics were obtained, including OA severity, knee pain, JSN, and alignment. We used 3D image processing techniques to obtain cyst parameters including: cyst number, cyst number per proximal tibial volume, cyst volume per proximal tibial volume, as well as maximum and average cyst volume across the proximal tibia, as well as regional bone mineral density (BMD) excluding cysts. We used Spearman's correlation coefficients to explore associations between patient characteristics and cyst parameters.ResultsAt both the medial and lateral compartments of the proximal tibia, greater cyst number and volume were associated with higher BMD. At the lateral region, cyst number and volume were also associated with lateral OA severity, lateral JSN, alignment and sex. Pain was not associated with any cyst parameters at any region.ConclusionCyst number and volume were associated with BMD at both the medial and lateral compartments. Lateral cyst number and volume were also associated with joint alignment, OA severity, JSN and sex. This is the first study to use clinical QCT to explore subchondral tibial cysts in patients with knee OA and provides further evidence of the relationships between subchondral cysts and clinical OA characteristics.

Project description:ObjectivesAccurate description of buccal bone adjacent to mandibular anterior teeth is helpful for planning and monitoring periodontal and orthodontic treatment. Low-dose cone beam computed tomography (LD-CBCT) imaging has shown promising results for very small dental structures in animals. This study asserts that LD-CBCT is sufficiently accurate to measure buccal alveolar bone adjacent to human mandibular anterior teeth.Materials and methodsBuccal bone level adjacent to 16 mandibular anterior teeth from four human cadavers was measured radiographically using one high-dose (HD) CBCT protocol and two LD-CBCT protocols. The resulting radiographic measurements of buccal bone height (bl) and thickness (bt) were compared with reference probe and reflected-light microscopy measurements. Measurement medians and Bland-Altman plots were calculated, and a linear mixed model was used to compare raters and imaging modalities.ResultsAll regression coefficients were approximately 0, indicating high interrater, intrarater, and intermodality agreement. No significant differences were found between reference measurements and CBCT protocols. The mean differences for bl measurements were 0.07 mm (rater 1 [r1]) and 0.12 mm (rater 2 [r2]) for HD-CBCT; 0.07 mm (r1) and 0.13 mm (r2) for LD-CBCT-1; and 0.02 mm (r1) and 0.01 mm (r2) for LD-CBCT-2. For bt measurements, mean differences were 0.02 mm (r1) and 0.02 mm (r2) for HD-CBCT; 0.01 mm (r1) and 0.01 mm (r2) for LD-CBCT-1; and 0.00 mm (r1) and 0.01 mm (r2) for LD-CBCT-2.ConclusionsWithin the limitations of the present study, LD-CBCT seems to be a precise method for describing buccal bone and its thickness adjacent to mandibular anterior teeth in this experimental setting.Clinical relevanceFor the first time, this study showed LD-CBCT produces excellent results and is a reliable modality for imaging buccal bone in vitro. If clinical studies confirm these results, LD-CBCT could enable better treatment planning and monitoring at a radiation dose that is far lower than that of conventional HD-CBCT but similar to that of panoramic views.

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Dose-dependent effects of genistein on bone homeostasis in rats' mandibular subchondral bone.

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Dose-dependent effects of genistein on bone homeostasis in rats' mandibular subchondral bone.

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