Related Experiment Video
Updated: Dec 12, 2025
Isolation of Mesenchymal Stem Cells from Human Alveolar Periosteum and Effects of Vitamin D on Osteogenic Activity of Periosteum-derived Cells
Published on: May 4, 2018
Overexpression of the vitamin D receptor (VDR) induces skeletal muscle hypertrophy
Joseph J Bass1, Asif Nakhuda1, Colleen S Deane2
1MRC/ARUK Centre for Musculoskeletal Ageing Research and National Institute for Health Research (NIHR), Nottingham Biomedical Research Centre (BRC), School of Medicine, University of Nottingham, DE22 3DT, UK.
Objective:
The Vitamin D receptor (VDR) has been positively associated with skeletal muscle mass, function and regeneration. Mechanistic studies have focused on the loss of the receptor, with in vivo whole-body knockout models demonstrating reduced myofibre size and function and impaired muscle development. To understand the mechanistic role upregulation of the VDR elicits in muscle mass/health, we studied the impact of VDR over-expression (OE) in vivo before exploring the importance of VDR expression upon muscle hypertrophy in humans.
Methods:
Wistar rats underwent in vivo electrotransfer (IVE) to overexpress the VDR in the Tibialis anterior (TA) muscle for 10 days, before comprehensive physiological and metabolic profiling to characterise the influence of VDR-OE on muscle protein synthesis (MPS), anabolic signalling and satellite cell activity. Stable isotope tracer (D2O) techniques were used to assess sub-fraction protein synthesis, alongside RNA-Seq analysis. Finally, human participants underwent 20 wks of resistance exercise training, with body composition and transcriptomic analysis.
Results:
Muscle VDR-OE yielded total protein and RNA accretion, manifesting in increased myofibre area, i.e., hypertrophy. The observed increases in MPS were associated with enhanced anabolic signalling, reflecting translational efficiency (e.g., mammalian target of rapamycin (mTOR-signalling), with no effects upon protein breakdown markers being observed. Additionally, RNA-Seq illustrated marked extracellular matrix (ECM) remodelling, while satellite cell content, markers of proliferation and associated cell-cycled related gene-sets were upregulated. Finally, induction of VDR mRNA correlated with muscle hypertrophy in humans following long-term resistance exercise type training.
Conclusion:
VDR-OE stimulates muscle hypertrophy ostensibly via heightened protein synthesis, translational efficiency, ribosomal expansion and upregulation of ECM remodelling-related gene-sets. Furthermore, VDR expression is a robust marker of the hypertrophic response to resistance exercise in humans. The VDR is a viable target of muscle maintenance through testable Vitamin D molecules, as active molecules and analogues.
Insights
Overexpressing the Vitamin D receptor (VDR) in rats stimulates muscle growth by increasing protein synthesis and cell activity. VDR levels also correlate with muscle hypertrophy in humans undergoing resistance training.
Area of Science:
- Muscle physiology and molecular biology.
- Endocrinology and metabolic research.
Background:
- The Vitamin D receptor (VDR) is linked to skeletal muscle mass and function.
- Previous research focused on VDR deficiency; this study investigates VDR upregulation's effects.
- Understanding VDR's role in muscle health is crucial for developing therapeutic strategies.
Purpose of the Study:
- To investigate the impact of VDR overexpression (OE) on muscle mass and health in vivo.
- To explore the mechanistic role of VDR upregulation in muscle hypertrophy.
- To determine the correlation between VDR expression and muscle hypertrophy in humans.
Main Methods:
- In vivo electrotransfer was used to overexpress VDR in rat muscle.
- Physiological and metabolic profiling assessed muscle protein synthesis (MPS), anabolic signaling, and satellite cell activity.
- Stable isotope tracers (D2O) and RNA-Seq analyzed protein synthesis and gene expression. Human participants underwent resistance training with body composition and transcriptomic analysis.
Main Results:
- VDR overexpression led to muscle hypertrophy, characterized by increased myofiber area and protein accretion.
- Enhanced anabolic signaling, particularly mTOR signaling, and increased translational efficiency were observed.
- Upregulation of satellite cell proliferation markers and extracellular matrix (ECM) remodeling genes was evident.
- VDR mRNA induction correlated with muscle hypertrophy in humans after resistance exercise training.
Conclusions:
- VDR overexpression promotes muscle hypertrophy through increased protein synthesis, ribosomal expansion, and ECM remodeling.
- VDR expression serves as a reliable indicator of the hypertrophic response to resistance exercise in humans.
- The VDR represents a potential therapeutic target for muscle maintenance using Vitamin D analogs.
Related Concept Videos
01:23Role of Skin in Vitamin D Synthesis
The solar UV B rays (290-315 nm) are absorbed by the skin, and 7-dehydrocholesterol (provitamin D3) photolyzes it to previtamin D3, which undergoes a rapid transformation to vitamin...
01:17Hormones and Bone Tissue
Hormones That Influence Osteoblasts and/or Maintain the Matrix
Several hormones are necessary for controlling bone growth and maintaining the bone matrix. The pituitary gland secretes growth hormone (GH), which, as its name implies, controls bone growth. This happens in several ways: first, it triggers chondrocyte...
01:16TGF - β Signaling Pathway
01:25Role of Vitamins in Maintaining Bone Health
Vitamin A
Vitamin A is involved in the process of bone remodeling. Retinoic acid, the active metabolite of Vitamin A, has nuclear receptors in osteoblasts and osteoclasts, which are involved in bone remodeling.
Vitamin B12
Vitamin B12 acts as a cofactor during the formation of osteoblast-related proteins, such as osteocalcin. Vitamin B12 plays a role...
02:23Master Transcription Regulators
01:21Satellite Stem Cells and Muscular Dystrophy