Age- and Strain-Related Differences in Bone Microstructure and Body Composition During Development in Inbred Male Mouse Strains

Papageorgiou, Maria; Föger-Samwald, Ursula; Wahl, Katharina; Kerschan‐Schindl, Katharina; Pietschmann, Péter

doi:10.1007/s00223-019-00652-8

Cited by 23 publications

(25 citation statements)

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“…These data are consistent with the results of others [14,15] and our previous work in male mice [18], showing that trabecular and cortical bone compartments are differentially affected by age. With regard to time related changes of individual parameters, no notable differences were seen between female mice investigated in this study and male mice investigated in our previous work [18]. No conclusions can be derived about the timing of peak cortical bone development in relation to peak muscle development, as our results suggest a peak of cortical bone accrual at 16 weeks or later.…”

Section: Discussionsupporting

confidence: 94%

“…Several studies report age-and strain-related variations in bone and muscle traits in inbred mice [12][13][14][15][16]. However, only a limited number of studies concomitantly investigated bone and muscle development [17,18]. In a recent study we explored age-related changes and strain-related differences in bone microstructure and body composition during growth in three commonly used male inbred mice strains [18].…”

Section: Introductionmentioning

confidence: 99%

“…However, only a limited number of studies concomitantly investigated bone and muscle development [17,18]. In a recent study we explored age-related changes and strain-related differences in bone microstructure and body composition during growth in three commonly used male inbred mice strains [18]. Given that osteoporotic risk later in life is higher in women than in men, valuable insights will be further gained from studying the muscle-bone connection in female mice.…”

Section: Introductionmentioning

confidence: 99%

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Bone and muscle development in three inbred female mouse strains

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Muscle force is thought to be one of the main determinants of bone development. Hence, peak muscle growth is expected to precede peak bone growth. In this study, we investigated muscle and bone development in female C57BL/6 J, DBA/2JRj, and C3H/HeOuJ mice. Femoral cortical and trabecular bone structure and the weights of selected muscles were assessed at the ages of 8, 16, and 24 weeks. Muscle mass increased from 8 to 24 weeks in all 3 strains, suggesting peak muscle development at 24 weeks or later. Bone volume fraction, trabecular number, and connectivity density of the femur decreased or remained unchanged, whereas trabecular density and trabecular thickness largely increased. These results suggest a peak in trabecular bone accrual at 8 weeks or earlier followed by further increases in density and structural reorganization of trabeculae. Cortical density, cortical thickness, and cortical cross sectional area increased over time, suggesting a peak in cortical bone accrual at 24 weeks or later. In conclusion, our data provide evidence that growth of muscle lags behind trabecular bone accrual.

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Section: Discussionsupporting

confidence: 94%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Bone and muscle development in three inbred female mouse strains

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“…Genetic factors have been reported to modulate various aspects of bone physiology, including the peak bone mass, bone structure, and bone composition 36 . Animal models have been established as valuable tools for experimentally defining the genetic regulation of bone mass and identifying the genetic determinants of bone structure that have been validated in humans 37,38 . In particular, inbred mice that have a homogeneous genetic background are useful models for studying genetic effects on bone structure and for examining variations in bone phenotypes under strictly controlled environmental conditions 37 .…”

Section: Discussionmentioning

confidence: 99%

Metabolic activities affect femur and lumbar vertebrae remodeling, and anti-resorptive risedronate disturbs femoral cortical bone remodeling

et al. 2021

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Metabolic activities are closely correlated with bone remodeling and long-term anti-resorptive bisphosphonate treatment frequently causes atypical femoral fractures through unclear mechanisms. To explore whether metabolic alterations affect bone remodeling in femurs and lumbar vertebrae and whether anti-osteoporotic bisphosphonates perturb their reconstruction, we studied three mouse strains with different fat and lean body masses (BALB/c, C57BL6, and C3H mice). These mice displayed variable physical activity, food and drink intake, energy expenditure, and respiratory quotients. Following intraperitoneal calcein injection, double calcein labeling of the femoral diaphysis, as well as serum levels of the bone-formation marker procollagen type-I N-terminal propeptide and the bone-resorption marker C-terminal telopeptide of type-I collagen, revealed increased bone turnover in mice in the following order: C3H > BALB/c ≥ C57BL6 mice. In addition, bone reconstitution in femurs was distinct from that in lumbar vertebrae in both healthy control and estrogen-deficient osteoporotic mice with metabolic perturbation, particularly in terms of femoral trabecular and cortical bone remodeling in CH3 mice. Interestingly, subcutaneous administration of bisphosphonate risedronate to C3H mice with normal femoral bone density led to enlarged femoral cortical bones with a low bone mineral density, resulting in bone fragility; however, this phenomenon was not observed in mice with ovariectomy-induced femoral cortical bone loss. Together, these results suggest that diverse metabolic activities support various forms of bone remodeling and that femur remodeling differs from lumbar vertebra remodeling. Moreover, our findings imply that the adverse effect of bisphosphonate agents on femoral cortical bone remodeling should be considered when prescribing them to osteoporotic patients.

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“…The C3H/HeJ mouse strain is characterised by high and sustained peak bone mass (17,21,38) and exhibits robust trabecular bone loss at 4 weeks post-OVX (21) . It is also the only strain reported to have a significant decrease in cortical area and width at 4 weeks post-OVX, and increased intracortical resorption spaces at 8 weeks post-OVX (18) .…”

Section: Introductionmentioning

confidence: 99%

Osteomacs support osteoclast-mediated resorption and contribute to bone pathology in a postmenopausal osteoporosis mouse model

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Millard

Raggatt

et al. 2021

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Osteal macrophages (osteomacs) support osteoblast function and promote bone anabolism, but their contribution to osteoporosis has not been explored. While mouse ovariectomy models have been repeatedly used, variation in strain, experimental design and assessment modalities, have contributed to no single model being confirmed as comprehensively replicating the full gamut of osteoporosis pathological manifestations. We validated an ovariectomy model in adult C3H/HeJ mice and demonstrated that it presents with human post-menopausal osteoporosis features, including reduced bone volume in axial and appendicular bone and bone loss in both trabecular and cortical bone including increased cortical porosity. Bone loss was associated with increased osteoclasts on trabecular and endocortical bone and decreased osteoblasts on trabecular bone. Importantly, this OVX model was characterised by delayed fracture healing. Using this validated model, we demonstrated that osteomacs are increased post-ovariectomy on both trabecular and endocortical bone. Dual F4/80 (pan-macrophage marker) and TRAP staining revealed osteomacs frequently located near TRAP+ osteoclasts and containing TRAP+ intracellular vesicles. Using an in vivo inducible macrophage depletion model that does not simultaneously deplete osteoclasts, we observed that osteomac loss was associated with elevated extracellular TRAP in bone marrow interstitium and increased serum TRAP. Using in vitro high-resolution confocal imaging of mixed osteoclast-macrophage cultures on bone substrate, we observed macrophages juxtaposed to osteoclast basolateral functional secretory domains scavenging degraded bone by-products. These data demonstrate a role for osteomacs in supporting osteoclastic bone resorption through phagocytosis and sequestration of resorption by-products. Finally, using Siglec1 knockout mice, we demonstrated that loss of the macrophage-restricted molecule Siglec-1/CD169 is sufficient to cause age-associated low bone mass, emphasizing the macrophages, independent of osteoclasts, contribute to optimal skeletal health. Overall, our data expose a novel role for osteomacs in supporting osteoclast function and provide the first evidence of their involvement in osteoporosis pathogenesis.

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Age- and Strain-Related Differences in Bone Microstructure and Body Composition During Development in Inbred Male Mouse Strains

Cited by 23 publications

References 50 publications

Bone and muscle development in three inbred female mouse strains

Bone and muscle development in three inbred female mouse strains

Metabolic activities affect femur and lumbar vertebrae remodeling, and anti-resorptive risedronate disturbs femoral cortical bone remodeling

Osteomacs support osteoclast-mediated resorption and contribute to bone pathology in a postmenopausal osteoporosis mouse model

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