A Site-Specific Comparison of the Trabecular Structure in Senescence-Accelerated Mice^|^mdash;Evaluation of Time-Course Changes in Bone Architecture using in Vivo Micro-CT^|^mdash;

Noguchi, Taku; Matsunaga, Satoru; Kinoshita, Hideaki; Fukuda, Masayuki; Saka, Hideki; Ide, Yoshinobu; Abe, Shinichi

doi:10.2485/jhtb.22.171

Cited by 3 publications

(4 citation statements)

References 19 publications

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“…The findings of the present study on OVX 16-week-old SAMP6 and SAMR1 mice showed that BV/TV and Tb.N were significantly lower in the Group A mice sacrificed 1 week after OVX, but did not reveal any differences in the trabecular structure of the Group C and Group D mice sacrificed 4 weeks after OVX. Our data from the 17-and 20-week-old SAMP6 and SAMR1 mice under the same experimental conditions of Noguchi indicated that there was a characteristically rapid and significant decrease in trabecular bone after OVX 9) , but that this decrease tapered off in the SAMP6 mice 4 weeks after OVX to a similar level of standard OVX mice. Timewise comparison of the same mouse strains showed that the Group A mice had significantly higher BV/TV, Tb.Th, and Tb.N values than in Group C, and that Group B had significantly higher BV/TV and Tb.N values than in Group D. This finding suggests that OVX SAMP6 mice have finer trabecular thickness than that of standard SAMP6 mice.…”

Section: Discussionmentioning

confidence: 81%

“…Studies by Noguchi et al and Chen et al have already shown that tibial trabecular structure is significantly thinner in SAMP6 mice than in their SAMR1 counterparts 9,18) . The findings of the present study on OVX 16-week-old SAMP6 and SAMR1 mice showed that BV/TV and Tb.N were significantly lower in the Group A mice sacrificed 1 week after OVX, but did not reveal any differences in the trabecular structure of the Group C and Group D mice sacrificed 4 weeks after OVX.…”

Section: Discussionmentioning

confidence: 99%

“…There still is particularly ongoing vigorous debate between researchers on the effects of osteoporosis on the jaw bone. Lee et al and Nakamoto et al both described their attempts at early detection of osteoporosis using radiographic imaging in the field of clinical dentistry 7,8) Satoru Matsunaga et al: Structural Characteristics of Alveolar Bone in OVX SAMP6 Mice using osteoporosis senescence-accelerated mouse-prone 6 (SAMP6) mice to compare bone resorption sites in the tibia and jaw bone 9) . Atwood et al also found that tooth loss had a greater effect on bone resorption than aging in the jaw bone; therefore, many questions remain as to the impact of osteoporosis on alveolar bone 10,11) .…”

Section: Introductionmentioning

confidence: 99%

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Effect of Ovariectomy on the Tibia and Alveolar Bone in a Senescence-Accelerated Mouse-Prone 6 (SAMP6) Model

Matsunaga

Maki

Noguchi

et al. 2016

J. Hard Tissue Biology.

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Recent investigations on osteoporosis have led to a better understanding of the pathology and treatment of the disease. However, the decline in sex hormones that typically accompanies aging makes it difficult to separately investigate the complex factors that cause the disease in humans. Various animal-based studies have demonstrated the pathology of senile osteoporosis (SO) and postmenopausal osteoporosis (PO), but a number of uncertainties remain as to the pathology behind the occurrence of both conditions. In the present study, we prepared ovariectomized senescence-accelerated mouse-prone 6 (SAMP6) mice and investigated the site specificity of trabecular structural properties in alveolar and tibial bone. The experimental animals were the SAMP6 mice (n = 10), while SAM-resistant/1 (SAMR1) mice (n = 10) served as controls. All mice were ovariectomized at 16 weeks of age and sacrificed at Week 17 and 20. The tibia and mandible bone samples were extracted and scanned using micro-computed tomography and subjected to bone morphometry. The results showed that trabecular bone was significantly thinner in the ovariectomized SAMP6 mice than in the ovariectomized SAMR1 mice at 17 weeks, but at 20 weeks, there were no significant differences in the tibial bone. In terms of alveolar bone, there were no significant differences in bone morphometry findings at week 17 but bone volume fraction and trabecular bone pattern factor values were significantly lower in the ovariectomized SAMP6 mice than in the ovariectomized SAMR1 mice at 20 weeks. The results therefore suggest that single onset of either PO or SO has little impact on alveolar bone but complex SO/PO onset causes severe alveolar bone resorption.

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Section: Discussionmentioning

confidence: 81%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Effect of Ovariectomy on the Tibia and Alveolar Bone in a Senescence-Accelerated Mouse-Prone 6 (SAMP6) Model

Matsunaga

Maki

Noguchi

et al. 2016

J. Hard Tissue Biology.

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“…The region of interest (ROI) was 1-mm-thick and positioned 0.5 mm above the growth plate. Bone mineral density, bone volume/tissue volume, trabecular number, trabecular thickness, trabecular separation, and marrow space star volume were semi-automatically determined in accordance with the guidelines for evaluation of bone microstructure using 3D images [24,25].…”

Section: Morphometric Evaluation Of Trabecular Bonementioning

confidence: 99%

High-Level Expression of Alkaline Phosphatase by Adeno-Associated Virus Vector Ameliorates Pathological Bone Structure in a Hypophosphatasia Mouse Model

et al. 2020

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Hypophosphatasia (HPP) is a systemic skeletal disease caused by mutations in the gene encoding tissue-nonspecific alkaline phosphatase (TNALP). We recently reported that survival of HPP model mice can be prolonged using an adeno-associated virus (AAV) vector expressing bone-targeted TNALP with deca-aspartate at the C terminus (TNALP-D 10); however, abnormal bone structure and hypomineralization remained in the treated mice. Here, to develop a more effective and clinically applicable approach, we assessed whether transfection with TNALP-D 10 expressing virus vector at a higher dose than previously used would ameliorate bone structure defects. We constructed a self-complementary AAV8 vector expressing TNALP driven by the chicken beta-actin (CBA) promoter (scAAV8-CB-TNALP-D 10). The vector was injected into both quadriceps femoris muscles of newborn HPP mice at a dose of 4.5 × 10 12 vector genome (v.g.)/body, resulting in 20 U/mL of serum ALP activity. The 4.5 × 10 12 v.g./body-treated HPP mice grew normally and displayed improved bone structure at the knee joints in X-ray images. Micro-CT analysis showed normal trabecular bone structure and mineralization. The mechanical properties of the femur were also recovered. Histological analysis of the femurs demonstrated that ALP replacement levels were sufficient to promote normal, growth plate cartilage arrangement. These results suggest that AAV vector-mediated high-dose TNALP-D 10 therapy is a promising option for improving the quality of life (QOL) of patients with the infantile form of HPP. Keywords Hypophosphatasia • Adeno-associated virus vector • Enzyme replacement therapy • Alkaline phosphatase • Bone structure Abbreviations AAV Adeno-associated virus ALP Alkaline phosphatase CBA Chicken beta-actin EGFP Enhanced green fluorescence protein Electronic supplementary material The online version of this article (

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Treatment of hypophosphatasia by muscle-directed expression of bone-targeted alkaline phosphatase via self-complementary AAV8 vector

Nakamura-Takahashi

Miyake

Watanabe

et al. 2016

Molecular Therapy - Methods & Clinical Development

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Hypophosphatasia (HPP) is an inherited disease caused by genetic mutations in the gene encoding tissue-nonspecific alkaline phosphatase (TNALP). This results in defects in bone and tooth mineralization. We recently demonstrated that TNALP-deficient (Akp2−/−) mice, which mimic the phenotype of the severe infantile form of HPP, can be treated by intravenous injection of a recombinant adeno-associated virus (rAAV) expressing bone-targeted TNALP with deca-aspartates at the C-terminus (TNALP-D10) driven by the tissue-nonspecific CAG promoter. To develop a safer and more clinically applicable transduction strategy for HPP gene therapy, we constructed a self-complementary type 8 AAV (scAAV8) vector that expresses TNALP-D10 via the muscle creatine kinase (MCK) promoter (scAAV8-MCK-TNALP-D10) and examined the efficacy of muscle-directed gene therapy. When scAAV8-MCK-TNALP-D10 was injected into the bilateral quadriceps of neonatal Akp2−/− mice, the treated mice grew well and survived for more than 3 months, with a healthy appearance and normal locomotion. Improved bone architecture, but limited elongation of the long bone, was demonstrated on X-ray images. Micro-CT analysis showed hypomineralization and abnormal architecture of the trabecular bone in the epiphysis. These results suggest that rAAV-mediated, muscle-specific expression of TNALP-D10 represents a safe and practical option to treat the severe infantile form of HPP.

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A Site-Specific Comparison of the Trabecular Structure in Senescence-Accelerated Mice^|^mdash;Evaluation of Time-Course Changes in Bone Architecture using in Vivo Micro-CT^|^mdash;

Cited by 3 publications

References 19 publications

Effect of Ovariectomy on the Tibia and Alveolar Bone in a Senescence-Accelerated Mouse-Prone 6 (SAMP6) Model

Effect of Ovariectomy on the Tibia and Alveolar Bone in a Senescence-Accelerated Mouse-Prone 6 (SAMP6) Model

High-Level Expression of Alkaline Phosphatase by Adeno-Associated Virus Vector Ameliorates Pathological Bone Structure in a Hypophosphatasia Mouse Model

Treatment of hypophosphatasia by muscle-directed expression of bone-targeted alkaline phosphatase via self-complementary AAV8 vector

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