ArticlePloS one2012
Tibial loading increases osteogenic gene expression and cortical bone volume in mature and middle-aged mice.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
43 citing papers in PubMed, 1 synthesis or guideline pooled it, 69 citations in OpenAlex.
- Methodological aspects ofJournal of musculoskeletal & neuronal interactions · 2023Pooled it
- Biomechanical comparison of mini-plate and screw fixation in minimally invasive distal metatarsal osteotomy for hallux valgus : a finite element and cadaveric study.Bone & joint research · 2026Article
- Sustained and reversible effects of a dietary phosphate intake on bone and mineral metabolism during aging.GeroScience · 2026Article
- Epigenetic Regulation ofInternational journal of molecular sciences · 2025Article
- Tibial Biomechanics and Adaptive Response to Mechanical Stimuli in the Green Iguana.Integrative organismal biology (Oxford, England) · 2025Article
- Article
- Cortical and Trabecular Bone Modeling and Implications for Bone Functional Adaptation in the Mammalian Tibia.Bioengineering (Basel, Switzerland) · 2024Review
- Article
- A novel framework for elucidating the effect of mechanical loading on the geometry of ovariectomized mouse tibiae using principal component analysis.Frontiers in bioengineering and biotechnology · 2024Article
- Article
- Unraveling the physiologic paradoxes that underlie exercise prescription for stress fracture prevention.Experimental biology and medicine (Maywood, N.J.) · 2022Review
- Similarities Between Disuse and Age-Induced Bone Loss.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2022Review
- Disrupted osteocyte connectivity and pericellular fluid flow in bone with aging and defective TGF-β signaling.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Article
- Mechanical stimuli and matrix properties modulate cancer spheroid growth in three-dimensional gelatin culture.Journal of the Royal Society, Interface · 2020Article
- Hallmarks of frailty and osteosarcopenia in prematurely aged PolgAJournal of cachexia, sarcopenia and muscle · 2020Article
- Diffuse microdamage in bone activates anabolic response by osteoblasts via involvement of voltage-gated calcium channels.Journal of bone and mineral metabolism · 2020Article
- Spaceflight-Induced Bone Tissue Changes that Affect Bone Quality and Increase Fracture Risk.Current osteoporosis reports · 2020Review
- Murine Axial Compression Tibial Loading Model to Study Bone Mechanobiology: Implementing the Model and Reporting Results.Journal of orthopaedic research : official publication of the Orthopaedic Research Society · 2020Review
- Detection of the Strains Induced in Murine Tibias by Ex Vivo Uniaxial Loading with Different Sensors.Sensors (Basel, Switzerland) · 2019Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
There are conflicting data on whether age reduces the response of the skeleton to mechanical stimuli. We examined this question in female BALB/c mice of different ages, ranging from young to middle-aged (2, 4, 7, 12 months). We first assessed markers of bone turnover in control (non-loaded) mice. Serum osteocalcin and CTX declined significantly from 2 to 4 months (p<0.001). There were similar age-related declines in tibial mRNA expression of osteoblast- and osteoclast-related genes, most notably in late osteoblast/matrix genes. For example, Col1a1 expression declined 90% from 2 to 7 months (p<0.001). We then assessed tibial responses to mechanical loading using age-specific forces to produce similar peak strains (-1300 µε endocortical; -2350 µε periosteal). Axial tibial compression was applied to the right leg for 60 cycles/day on alternate days for 1 or 6 weeks. qPCR after 1 week revealed no effect of loading in young (2-month) mice, but significant increases in osteoblast/matrix genes in older mice. For example, in 12-month old mice Col1a1 was increased 6-fold in loaded tibias vs. controls (p = 0.001). In vivo microCT after 6 weeks revealed that loaded tibias in each age group had greater cortical bone volume (BV) than contralateral control tibias (p<0.05), due to relative periosteal expansion. The loading-induced increase in cortical BV was greatest in 4-month old mice (+13%; p<0.05 vs. other ages). In summary, non-loaded female BALB/c mice exhibit an age-related decline in measures related to bone formation. Yet when subjected to tibial compression, mice from 2-12 months have an increase in cortical bone volume. Older mice respond with an upregulation of osteoblast/matrix genes, which increase to levels comparable to young mice. We conclude that mechanical loading of the tibia is anabolic for cortical bone in young and middle-aged female BALB/c mice.
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Registered trials
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