The effects of different intensities of exercise and active vitamin D on mouse bone mass and bone strength

Zhang, Lingli; Chen, Xi; Wu, Juanni; Yuan, Yu; Guo, Jianmin; Biswas, Soma; Li, Baojie; Zou, Jun

doi:10.1007/s00774-016-0764-9

Cited by 19 publications

(17 citation statements)

References 67 publications

(73 reference statements)

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“…Our previous studies showed that moderate exercise could promote bone formation and inhibit bone resorption, thus increase the BMD, microstructure and biomechanical characteristics of bone in young mice [26]. In the present study, exercise was shown to improve the BMD and microstructure parameters of tibia (▶Fig.…”

Section: Moderate Exercise Inhibits the Expression Of Mir-214 In Bonesupporting

confidence: 53%

“…In vivo studies have shown that exercise increases bone mass, BMD and bone strength, and improves bone microstructure in both humans and animals [7,[26][27][28]. In vitro studies have also reported that mechanical loading enhances osteogenic differentiation and inhibits bone resorption through regulating bone anabolic and anti-catabolic gene expression, thus improving bone metabolism and promoting bone formation [9,29,30].…”

Section: Discussionmentioning

confidence: 99%

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MiR-214 Attenuates the Osteogenic Effects of Mechanical Loading on Osteoblasts

et al. 2019

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Exercise is an effective way to prevent osteoporosis, but its mechanism remains unclear. MicroRNAs (miRNAs) play an essential role in bone metabolism. Recently, mechanical loading was reported to induce changes in miRNA expression in osteoblasts. However, the role of miRNAs in bone under exercise and its underlining mechanisms of action still remain unknown. MiR-214 was reported to regulate the process of osteogenesis and is considered a biomarker of osteoporosis. In this study, we aimed to investigate whether exercise could induce changes in miRNA expression in bone and to study the effects of miR-214 on mechanical loading-induced osteogenesis in osteoblasts. The results showed that miR-214 was down-regulated in both tibia from C57BL/6 mice after exercise in vivo and in osteoblasts after mechanical strain in vitro. Mechanical strain could enhance the ALP activity, promote matrix mineralization, up-regulate the expression of osteogenic factors such as ATF4, Osterix, ALP and β-catenin, and down-regulate RANKL and RANK expression. Over-expression of miR-214 not only inhibited the expression of these osteogenic factors but also attenuated mechanical strain-enhanced osteogenesis in osteoblasts. Collectively, our results indicated that miR-214 could attenuate the osteogenic effects of mechanical loading on osteoblasts, suggesting that inhibition of miR-214 may be one of the ways in which exercise prevents osteoporosis.

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Section: Moderate Exercise Inhibits the Expression Of Mir-214 In Bonesupporting

confidence: 53%

Section: Discussionmentioning

confidence: 99%

MiR-214 Attenuates the Osteogenic Effects of Mechanical Loading on Osteoblasts

et al. 2019

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“…Subtle variations between the exercise protocols used in ours and previous work may have contributed to the lack of effect observed. Recent work studying the effects of exercise on bone mass in wild type C57BL/6 mice shows that the intensity of exercise is critical with no significant increase in bone mass occurring when intensity is too low or too high 73 . The authors suggest that a minimum threshold of exercise must be reached to achieve a positive effect on bone density accrual and hypothesise that increased free radical production with excessive exercise, impairs bone mass accumulation.…”

Section: Discussionmentioning

confidence: 99%

Mitochondrial dysfunction impairs osteogenesis, increases osteoclast activity, and accelerates age related bone loss

Dobson

Dennis

Hipps

et al. 2020

Sci Rep

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The pathogenesis of declining bone mineral density, a universal feature of ageing, is not fully understood. Somatic mitochondrial DNA (mtDNA) mutations accumulate with age in human tissues and mounting evidence suggests that they may be integral to the ageing process. To explore the potential effects of mtDNA mutations on bone biology, we compared bone microarchitecture and turnover in an ageing series of wild type mice with that of the PolgA mut/mut mitochondrial DNA ‘mutator’ mouse. In vivo analyses showed an age-related loss of bone in both groups of mice; however, it was significantly accelerated in the PolgA mut/mut mice. This accelerated rate of bone loss is associated with significantly reduced bone formation rate, reduced osteoblast population densities, increased osteoclast population densities, and mitochondrial respiratory chain deficiency in osteoblasts and osteoclasts in PolgA mut/mut mice compared with wild-type mice. In vitro assays demonstrated severely impaired mineralised matrix formation and increased osteoclast resorption by PolgA mut/mut cells. Finally, application of an exercise intervention to a subset of PolgA mut/mut mice showed no effect on bone mass or mineralised matrix formation in vitro. Our data demonstrate that mitochondrial dysfunction, a universal feature of human ageing, impairs osteogenesis and is associated with accelerated bone loss.

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“…This is also consistent with the medium-intensity inhibited bone resorption and increased bone formation in young mice femur, which resulted in the improvements in the mineral density, trabecular BV, and strength. 13 Based on the discussions, this study could propose some suggestion for clinical or rehabilitation training applications. At the initial stage (in the first month), the mechanical stimulus almost produced no bone, and this was relatively consistent with the implants at early loading time within the first two or three weeks in dogs and monkeys.…”

Section: Discussionmentioning

confidence: 99%

“…12 However, excessive exercise was not beneficial for the bone formation, and a medium intensity was reported to optimize bone mass and strength via affecting both the bone formation and resorption in rats. 13 Although many cell and clinical experiments give qualitative conclusions or phenomena (e.g. effectiveness of treating bone diseases 14 or accuracy of testing methods in clinical use 15 ), to the best of the authors’ knowledge, very few work can be referred to reveal the bone formation starting from the cell levels, not even mention the quantitative description of the bone-repair process.…”

Section: Introductionmentioning

confidence: 99%

Mathematical modeling of bone in-growth into undegradable porous periodic scaffolds under mechanical stimulus

et al. 2019

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Undegradable scaffolds, as a key element in bone tissue engineering, prevail in the present clinical applications, and the bone in-growth into such scaffolds under mechanical stimulus is an important issue to evaluate the bone-repair effect. This work aims to develop a mathematical framework to investigate the effect of mechanical stimulus on the bone in-growth into undegradable scaffolds. First, the osteoclast and osteoblast activities were coupled by their autocrine and paracrine effects. Second, the mechanical stimulus was empirically incorporated into the coupling cell activities on the basis of experimental observations. Third, the effect of mechanical stimulus including intensity and duration on the bone in-growth process was numerically studied; moreover, the homeostasis of scaffold–bone system under the mechanical stimulus was also treated. The results showed that the numbers of osteoblasts and osteoclasts in the scaffold–bone system tended to constants representing the system homeostasis. Both the mechanical intensity and duration optimized the final bone formation. The numerical results of the bone formation were comparable to the experimental results in rats. The findings from this modeling study could be used to explain many physiological phenomena and clinical observations. The developed model integrates both cell and tissue scales, which can be used as a platform to investigate bone remodeling under mechanical stimulus.

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The effects of different intensities of exercise and active vitamin D on mouse bone mass and bone strength

Cited by 19 publications

References 67 publications

MiR-214 Attenuates the Osteogenic Effects of Mechanical Loading on Osteoblasts

MiR-214 Attenuates the Osteogenic Effects of Mechanical Loading on Osteoblasts

Mitochondrial dysfunction impairs osteogenesis, increases osteoclast activity, and accelerates age related bone loss

Mathematical modeling of bone in-growth into undegradable porous periodic scaffolds under mechanical stimulus

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