Micro-computed tomography assessment of bone structure in aging mice

Shim, Junbo; Iwaya, Chihiro; Ambrose, Catherine G.; Suzuki, Akiko; Iwata, Junichi

doi:10.1038/s41598-022-11965-4

Cited by 28 publications

(17 citation statements)

References 95 publications

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“…However, because cortical thickness and cortical area fraction were similar between basal and ground control groups, results suggest bone formation at the periosteal surface in combination with assumed endosteal resorption (29). This is typical for mice of this age (4-5 months) and represents normal skeletal remodeling (28,30). Nonetheless, mouse strain and age may be additional differentiating factors between results presented here and previous observations.…”

Section: Discussionmentioning

confidence: 75%

Characterization of the murine spine for spaceflight studies

Lim,

Veres,

Almeida

et al. 2024

Preprint

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Rodents provide a useful analog for understanding the effects of spaceflight on the human body, offering opportunities for investigations into the relationship between microgravity and the musculoskeletal system. In particular, rodents have often been utilized to improve our understanding of the effects of spaceflight on the spine, including intervertebral disc and vertebral body health. However, there are a number of experimental factors that differ between existing works, including mission duration, animal housing, and anatomical location of interest, making it difficult to draw holistic conclusions. Additionally, the quadrupedal nature of the murine spine results in different biomechanical loading than in a bipedal organism. Thus, the objective of this study was to more fully define the bulk properties of the murine lumbar spine model after 28 days of spaceflight. Additionally, the proximal tibia was analyzed to provide insight into the skeletal site-specificity of gravitational unloading in space. Results indicated that the effects of spaceflight on vertebral body bone microarchitecture, intervertebral disc biochemistry, and intervertebral disc joint mechanics were statistically insignificant, while large and significant bone loss was observed in the proximal tibia of the same animals. We hypothesize that this may be due to site-specific loading changes in space. Specifically, vigorous ambulatory behaviors observed in this experiment after initial acclimation to spaceflight may increase axial load-bearing in the lumbar spine, while maintaining microgravity induced mechanical unloading in the tibia. In total, this work shows that the rodent spine, unlike the weight bearing tibia in the same mice, is not affected by gravitational unloading, suggesting the tissue degenerative effects of spaceflight are site- and load-specific and not systemic. This study also highlights the importance of considering experimental variables such as habitat acclimation, physical activity, and experiment duration as key factors in determining musculoskeletal and spine health outcomes during spaceflight.

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Section: Discussionmentioning

confidence: 75%

Characterization of the murine spine for spaceflight studies

Lim,

Veres,

Almeida

et al. 2024

Preprint

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“…Object Research Systems (ORS) Inc., Montreal, Canada] with DICOM files. Craniofacial bones were isolated and labeled using the Dragonfly’s semiautomatic segmentation editor 19 , 20 . The square root of the sum of the squared distances from the centroid of the landmark configuration to each landmark was quantified as the deviation of the landmark configuration of each specimen.…”

Section: Methodsmentioning

confidence: 99%

Craniofacial bone anomalies related to cholesterol synthesis defects

Iwaya,

Suzuki,

Shim

et al. 2024

Sci Rep

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DHCR7 and SC5D are enzymes crucial for cholesterol biosynthesis, and mutations in their genes are associated with developmental disorders, which are characterized by craniofacial deformities. We have recently reported that a loss of either Dhcr7 or Sc5d results in a failure in osteoblast differentiation. However, it remains unclear to what extent a loss of function in either DHCR7 or SC5D affects craniofacial skeletal formation. Here, using micro computed tomography (μCT), we found that the bone phenotype differs in Dhcr7−/− and Sc5d−/− mice in a location-specific fashion. For instance, in Sc5d−/− mice, although craniofacial bones were overall affected, some bone segments, such as the anterior part of the premaxilla, the anterior–posterior length of the frontal bone, and the main body of the mandible, did not present significant differences compared to WT controls. By contrast, in Dhcr7−/− mice, while craniofacial bones were not much affected, the frontal bone was larger in width and volume, and the maxilla and palatine bone were hypoplastic, compared to WT controls. Interestingly the mandible in Dhcr7−/− mice was mainly affected at the condylar region, not the body. Thus, these results help us understand which bones and how greatly they are affected by cholesterol metabolism aberrations in Dhcr7−/− and Sc5d−/− mice.

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“…Three‐dimensional images were reconstructed based on the micro‐CT scan images using NRecon software (Bruker), and the bone parameters were calculated using the CTAn program (Bruker). All analyses were performed using a volume of interest (VOI) in the micro‐CT scan images as previously shown (Shim et al, 2022). The VOI for the trabecular bone was determined at a height of 1 mm, which was 0.5 mm away from the growth plate in the distal femur and proximal tibia.…”

Section: Methodsmentioning

confidence: 99%

Gulp1 deficiency augments bone mass in male mice by affecting osteoclasts due to elevated 17β‐estradiol levels

Kim

Park

et al. 2023

Journal Cellular Physiology

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The engulfment adaptor phosphotyrosine‐binding domain containing 1 (GULP1) is an adaptor protein involved in the engulfment of apoptotic cells via phagocytosis. Gulp1 was first found to promote the phagocytosis of apoptotic cells by macrophages, and its role in various tissues, including neurons and ovaries, has been well studied. However, the expression and function of GULP1 in bone tissue are poorly understood. Consequently, to determine whether GULP1 plays a role in the regulation of bone remodeling in vitro and in vivo, we generated Gulp1 knockout (KO) mice. Gulp1 was expressed in bone tissue, mainly in osteoblasts, while its expression is very low in osteoclasts. Microcomputed tomography and histomorphometry analysis in 8‐week‐old male Gulp1 KO mice revealed a high bone mass in comparison with male wild‐type (WT) mice. This was a result of decreased osteoclast differentiation and function in vivo and in vitro as confirmed by a reduced actin ring and microtubule formation in osteoclasts. Gas chromatography‐mass spectrometry analysis further showed that both 17β‐estradiol (E2) and 2‐hydroxyestradiol levels, and the E2/testosterone metabolic ratio, reflecting aromatase activity, were also higher in the bone marrow of male Gulp1 KO mice than in male WT mice. Consistent with mass spectrometry analysis, aromatase enzymatic activity was significantly higher in the bone marrow of male Gulp1 KO mice. Altogether, our results suggest that GULP1 deficiency decreases the differentiation and function of osteoclasts themselves and increases sex steroid hormone‐mediated inhibition of osteoclast differentiation and function, rather than affecting osteoblasts, resulting in a high bone mass in male mice. To the best of our knowledge, this is the first study to explore the direct and indirect roles of GULP1 in bone remodeling, providing new insights into its regulation.

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Micro-computed tomography assessment of bone structure in aging mice

Cited by 28 publications

References 95 publications

Characterization of the murine spine for spaceflight studies

Characterization of the murine spine for spaceflight studies

Craniofacial bone anomalies related to cholesterol synthesis defects

Gulp1 deficiency augments bone mass in male mice by affecting osteoclasts due to elevated 17β‐estradiol levels

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