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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
Vitamin D Auto-/Paracrine System Is Involved in Modulation of Glucocorticoid-Induced Changes in Angiogenesis/Bone
Olha Lisakovska1, Ihor Shymanskyi1, Dmytro Labudzynskyi1
1Department of Biochemistry of Vitamins and Coenzymes, Palladin Institute of Biochemistry of the National Academy of Sciences of Ukraine, Kyiv, Ukraine.
Abstract:
Osteoporosis is a devastating side effect of chronic glucocorticoid (GC) treatment. Despite the crucial role of vitamin D (VD) in bone homeostasis, the precise molecular mechanisms of its action on GC-induced disturbances of bone remodeling remain undefined. The study was performed to elucidate the relation of VD status to GC-induced changes of the angiogenesis/osteogenesis/bone resorption coupling in bone tissue. Female Wistar rats received prednisolone (5 mg/kg of b.w.) with or without VD3 (1000 IU/kg of b.w., for 30 days). Biomechanical parameters of rat femurs were assessed by the three-point bending test. The levels of calcium, inorganic phosphate, activity of total alkaline phosphatase (ALP), and its isoenzymes were determined spectrophotometrically. Vascular endothelial growth factor-A (VEGF-A) and caspase-3 protein levels were detected by western blotting. Vdr and Cyp27b1 mRNAs were measured by qRT-PCR. Receptor activator of nuclear factor κB (RANK) expression in bone sections was visualized immunohistochemically. Serum 25(OH)D was assayed by ELISA. GC administration led to a decrease in maximal load (by 1.2-fold) and stiffness and toughness (by 1.3-fold), which was accompanied by a 3-fold reduction of 25(OH)D level, an elevation of the ALP bone isoenzyme activity in serum, hypocalcaemia, and hypophosphatemia. Along with prednisolone-induced VD deficiency, an impaired synthesis of Vdr (-30%) and Cyp27b1 (+71%) mRNA was observed, reflecting deregulation of bone tissue VD-auto-/paracrine system. GC caused an increase in caspase-3 content, suppressed the synthesis of the osteoclastic marker RANK, and altered angiogenesis/osteogenesis coupling by significantly reducing the level of VEGF-A.VD3 treatment restored serum 25(OH)D content and the expression of key components of the VD-auto-/paracrine system. VD3 supplementation diminished cell apoptosis and strongly improved angiogenesis/osteogenesis coupling as well as mineral metabolism and biomechanical parameters of femurs in GC-administered rats. Thus, VD3 can have a beneficial effect on the correction of GC-induced pathological changes in bone remodeling.
Insights
Vitamin D3 supplementation can counteract bone loss caused by glucocorticoids by improving bone remodeling, angiogenesis, and mineral metabolism. This study highlights vitamin D
Area of Science:
- Bone Biology and Metabolism
- Endocrinology
- Pharmacology
Background:
- Glucocorticoids (GCs) are essential medications but induce osteoporosis, a significant side effect.
- The role of vitamin D (VD) in bone homeostasis is established, yet its specific mechanisms in GC-induced bone disturbances are unclear.
- Understanding VD's impact on GC-affected bone remodeling is crucial for mitigating GC-induced bone loss.
Purpose of the Study:
- To investigate the relationship between vitamin D status and GC-induced alterations in bone remodeling.
- To elucidate how VD influences the coupling of angiogenesis, osteogenesis, and bone resorption under GC treatment.
- To assess the therapeutic potential of VD3 in preventing GC-induced bone pathology.
Main Methods:
- Prednisolone administration to female Wistar rats, with or without vitamin D3 supplementation.
- Assessment of femur biomechanical properties, serum mineral and alkaline phosphatase levels.
- Analysis of VEGF-A, caspase-3, VDR, Cyp27b1 mRNA, and RANK expression.
Main Results:
- Glucocorticoid treatment significantly reduced bone biomechanical parameters and serum 25(OH)D levels.
- GCs impaired VD auto/paracrine signaling, increased apoptosis (caspase-3), and reduced angiogenesis (VEGF-A) and osteoclast marker (RANK).
- Vitamin D3 supplementation normalized 25(OH)D, improved gene expression, reduced apoptosis, and enhanced bone mineral and biomechanical properties.
Conclusions:
- Vitamin D3 effectively mitigates GC-induced bone remodeling disturbances.
- VD3 supplementation restores angiogenesis/osteogenesis coupling and improves bone mineral and biomechanical integrity.
- Vitamin D3 demonstrates significant therapeutic potential for managing glucocorticoid-induced osteoporosis.
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