Abnormal bone regeneration induced by FK506 in medaka fin revealed by in vivo imaging.

OBJECTIVES: Bone tissue in bony fish demonstrates a remarkable ability to regenerate, particularly evident following induction of extensive bone defects, such as fin amputation. This regenerative capacity has been reported to be promoted by the immunosuppressant FK506, yet its precise effects on bone cells during fin regeneration remains insufficiently elucidated. This study aims to investigate the effects of FK506 treatment on bone morphology, osteoblasts, and osteoclasts in the bony fin rays of osterix promoter-DsRed/TRAP promoter-EGFP double transgenic (Tg) medaka. METHODS: The caudal fin of double Tg medaka was amputated, followed by a 20-day treatment with FK506 (1.0 µg/ml) to observe its effects on fin regeneration. Additionally, the regenerated caudal fin area underwent evaluation using genetic analysis and cell proliferation assays. RESULTS: FK506 treatment significantly increased osterix-positive osteoblast formation, resulting in both a significantly longer fin length and fewer joints in the bony fin rays formed during fin regeneration. Notably, TRAP-positive osteoclast formation and bone resorption were observed to occur primarily during the latter stages of fin regeneration. Furthermore, while the expression levels of osteoblast-related genes in the regenerated area remained unchanged following FK506 treatment, a heightened cell proliferation was observed at the tip of the fin. CONCLUSIONS: Our findings suggest that treatment with FK506 promotes bone regeneration by increasing the number of osteoblasts in the amputated area of the fin. However, long-term treatment disrupts regular bone metabolism by inducing abnormal osteoclast formation.

Tacrolimus, FK506, promotes bone formation in bone defect mouse model.

OBJECTIVES: Some studies have reported that tacrolimus (FK506), an immunosuppressant, may have positive effects on bone formation. However, the precise effects of FK506 on bone repair or osteoblasts remain inadequately elucidated, and limited research has explored the outcomes of its use in an in vivo mouse model. This study aims to examine the effects of FK506 on bone repair and osteoblast functions using bone defect and BMP-2-induced ectopic ossification mouse models, as well as cultured primary mouse osteoblasts treated with FK506. METHODS: We established mouse models of femur bone defect and BMP-2-induced ectopic ossification to evaluate the effect of FK506 on new bone formation, respectively. Additionally, primary mouse osteoblasts were cultured with FK506 and examined for gene expressions related to osteoblast differentiation. RESULTS: While FK506 promoted the repair of bone defect areas in the femur of the bone defect mouse model, it also led to widespread abnormal bone formation outside the intended area. Additionally, following the implantation of a collagen sponge containing BMP-2 into mouse muscle tissue, FK506 was found to promote ectopic ossification and enhance BMP-2-induced osteoblast differentiation in vitro. Our findings also revealed that FK506 increased the number of immature osteoblasts in the absence of BMP-2 without affecting osteoblast differentiation. Furthermore, direct effects were observed, reducing the ability of osteoblasts to support osteoclastogenesis. CONCLUSIONS: These results indicate that FK506 increases new bone formation during bone repair and influences the proliferation of immature osteoblasts, as well as osteoblast-supported osteoclastogenesis.

Serum KL-6 and surfactant protein D in children with 2009 pandemic H1N1 influenza infection.

BACKGROUND: A global pandemic influenza A (H1N1) outbreak occurred in 2009. Rapid progress of respiratory distress is one of the characteristic features of pandemic influenza A (H1N1) infection. The physiologic mechanism causing hypoxia in pandemic influenza A (H1N1) infection, however, has not been elucidated. METHODS: The serum levels of KL-6 and surfactant protein D (SP-D) were evaluated in 21 cases of pandemic influenza A (H1N1) infection associated with chest radiographic abnormality in order to estimate alveolar involvement. The clinical features were also analyzed. RESULTS: All of the patients had high fever, and rapidly progressed to respiratory distress within several days of disease onset. Despite mild radiographic abnormality in these patients, dyspnea was severe and they had low blood oxygen saturation levels. Many of the patients had a history of allergic diseases including asthma. Serum KL-6 and SP-D levels on admission were 191 ± 69 U/mL and 32.6 ± 18.9 ng/mL, respectively. These two levels were still below the upper normal limit 1 week later. There were no clear relationships between specific clinical symptoms and KL-6 or SP-D levels. All patients were treated with oseltamivir and/or zanamivir, and improved without mechanical ventilation management. CONCLUSION: KL-6 and SP-D elevation were not significant in pandemic influenza A (H1N1) infection associated with chest radiographic abnormality. In pandemic influenza A (H1N1) infection, alveolar involvement was estimated to be little, and severe respiratory distress was probably caused by obstruction of peripheral bronchi.

The accuracy of 3-dimensional magnetic resonance 3D vibe images of the mandible: an in vitro comparison of magnetic resonance imaging and computed tomography.

OBJECTIVE: The purpose of this study was to investigate in vitro the accuracy of three-dimensional (3D) magnetic resonance imaging (MRI) to measure the mandible. STUDY DESIGN: The optimal MRI sequence for 3D mandible from the data of 2 volunteers was determined to be 3D vibe. MRI and computed tomography (CT) scans of tube, mandible, and hemimandible phantoms were obtained. MRI with 3D vibe and standard parameters used in clinical practice for 3D reconstructions of jawbones on CT were used. Pearson's correlation coefficient, standard deviation (SD), and accuracy in measurement on reconstructed 3D MRI and CT were compared to direct osteometric measurement of the phantoms. RESULTS: The correlation coefficient between MRI and direct osteometry was high, with r = 0.85 to 0.99 (P < .001). The difference ranged from -1.5 to 0.7 mm (-8.9%-11.1%) on smaller distances, which is important for orthognathic surgery. The accuracy of MRI was similar to that of CT. CONCLUSION: 3D vibe MRI provided adequate dimensional accuracy and image quality during in vitro examination of the mandible.

Correlation of mandibular deviation with temporomandibular joint MR dimensions, MR disk position, and clinical symptoms.

OBJECTIVE: The objective of this study was to investigate the difference of the temporomandibular joint (TMJ) between deviated and nondeviated sides of the mandible in adult patients with mandibular deviation. STUDY DESIGN: TMJ size, disk displacement, and clinical symptoms of 28 patients were examined clinically and by magnetic resonance imaging (MRI). Twelve age- and sex-matched control subjects were also used to evaluate which side of the mandible in patients was similar to the control. RESULTS: The TMJ on the deviated side showed a smaller condyle and a higher incidence of disk displacement than the nondeviated side and those in the controls. However, the clinical symptoms showed no differences between the deviated and nondeviated sides, and no association with disk displacement. CONCLUSIONS: Our results suggest that the deviated side was the abnormal side and may have some association with mandibular deviation. However, the clinical symptoms could not indicate those differences.

Oxysterol regulation of estrogen receptor alpha-mediated gene expression in a transcriptional activation assay system using HeLa cells.

In order to test the estrogenic activity of sterol oxidation products from cholesterol and phytosterols, an estrogen-dependent gene expression assay was performed in estrogen receptor alpha-stably transformed HeLa cells. The ranking of the estrogenic potency of these compounds was different: 17beta-estradiol >> genistein >> beta-epoxycholesterol = daidzein = cholestanetriol = 22(R)-hydroxycholesterol = 20(S)-hydroxycholesterol = sitostanetriol > campestanetriol = beta-epoxysitosterol = 7beta-hydroxycholesterol. These compounds were not estrogenic in estrogen receptor-negative HeLa cells.