Mechanism of inhibitory action of Eldecalcitol, an active vitamin D analog, on bone resorption in vivo

2013 ◽  
Vol 136 ◽  
pp. 171-174 ◽  
Author(s):  
Naoyuki Takahashi
Keyword(s):  
Vitamin D ◽  
Bone Resorption ◽  
Inhibitory Action ◽  
Active Vitamin ◽  
Active Vitamin D ◽  
Vitamin D Analog

scholarly journals Active vitamin D (1,25-dihydroxyvitamin D3) increases host susceptibility toCitrobacter rodentiumby suppressing mucosal Th17 responses

2012 ◽  
Vol 303 (12) ◽  
pp. G1299-G1311 ◽  
Author(s):  
Natasha R. Ryz ◽  
Scott J. Patterson ◽  
Yiqun Zhang ◽  
Caixia Ma ◽  
Tina Huang ◽  
...  
Keyword(s):  
Vitamin D ◽  
Immune Responses ◽  
Bacterial Pathogen ◽  
Enteric Bacteria ◽  
Host Susceptibility ◽  
Active Vitamin ◽  
Active Vitamin D ◽  
Increased Risk ◽  
The Impact

Vitamin D deficiency affects more that 1 billion people worldwide and is associated with an increased risk of developing a number of inflammatory/autoimmune diseases, including inflammatory bowel disease (IBD). At present, the basis for the impact of vitamin D on IBD and mucosal immune responses is unclear; however, IBD is known to reflect exaggerated immune responses to luminal bacteria, and vitamin D has been shown to play a role in regulating bacteria-host interactions. Therefore, to test the effect of active vitamin D on host responses to enteric bacteria, we gave 1,25(OH)2D3to mice infected with the bacterial pathogen Citrobacter rodentium, an extracellular microbe that causes acute colitis characterized by a strong Th1/Th17 immune response. 1,25(OH)2D3treatment of infected mice led to increased pathogen burdens and exaggerated tissue pathology. In association with their increased susceptibility, 1,25(OH)2D3-treated mice showed substantially reduced numbers of Th17 T cells within their infected colons, whereas only modest differences were noted in Th1 and Treg numbers. In accordance with the impaired Th17 responses, 1,25(OH)2D3-treated mice showed defects in their production of the antimicrobial peptide REG3γ. Taken together, these studies show that 1,25(OH)2D3suppresses Th17 T-cell responses in vivo and impairs mucosal host defense against an enteric bacterial pathogen.

scholarly journals The Therapeutic Effect of Active Vitamin D Supplementation in Preventing the Progression of Diabetic Nephropathy in a Diabetic Mouse Model

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Nakhoul Nakhoul ◽  
Tina Thawko ◽  
Evgeny Farber ◽  
Inbal Dahan ◽  
Hagar Tadmor ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Vitamin D ◽  
Diabetic Nephropathy ◽  
Vitamin D Receptor ◽  
Receptor Activation ◽  
Receptor Expression ◽  
Active Vitamin ◽  
Active Vitamin D ◽  
Vitamin D Analog

Background. Diabetic nephropathy (DN) is one of the most common microvascular complications of diabetes and is the leading cause of end-stage renal disease (ESRD) and replacement therapy worldwide. Vitamin D levels in DN patients are very low due to the decrease in the synthesis and activity of 1-α hydroxylase in the proximal tubule cells and decrease in the vitamin D receptor abundance. To date, few studies have shown the antioxidant effects of 1α,25-dihydroxyvitamin D3 [1,25(OH)2D3] on hyperglycemia-induced renal injury. The selective activator of the vitamin D receptor, paricalcitol, reduces proteinuria and slows the progression of kidney injury. The precise mechanism through which vitamin D affects diabetic status and provides kidney protection remains to be determined. Methods. Diabetes mellitus (DM) was induced in 94 8-week-old DBA/2J mice by intraperitoneal injection of streptozotocin (STZ). DM mice were randomly divided into receiving vehicle or treatment with paricalcitol, the active vitamin D analog, 1 week after DM induction or paricalcitol treatment 3 weeks after DM induction. An additional control group of healthy wild-type mice was not treated. Urine albumin, blood urea nitrogen, and creatinine levels were measured before and at the end of the paricalcitol treatment. Periodic acid-Schiff, immunohistochemistry staining, and western blot of the renal tissues of vitamin D receptor, villin, nephrin, and podocin expressions, were analyzed. Results. Paricalcitol treatment restored villin, nephrin, and podocin protein levels that were downregulated upon DM induction, and reduced fibronectin protein level. Vitamin D receptor activation by paricalcitol may reduce proteinuria of DN in mice and alleviate high-glucose-induced injury of kidney podocytes by regulating the key molecules such nephrin-podocin. Conclusions. Paricalcitol treatment was associated with improved structural changes in type 1 diabetic mice including upregulation of vitamin D receptor expression, and decreased fibrosis markers such as fibronectin. These effects may contribute to the consistent benefit of vitamin D analog to slow the deterioration in glomerular function and reduce the risk of ESRD in patients with type 1 and 2 diabetes mellitus. Our results suggest that additional use of paricalcitol may be beneficial in treating patients with diabetes under standard therapeutic strategies.

MO058INHIBITION OF OSTEOCLAST DIFFERENTIATION BY 1.25-D AND THE CALCIMIMETIC KP2326 REVEALS 1.25-D RESISTANCE IN ADVANCED CKD

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Julie Bernardor ◽  
Sacha Flammier ◽  
Bruno Ranchin ◽  
Segolene Gaillard ◽  
Diane Platel ◽  
...  
Keyword(s):  
Vitamin D ◽  
Bone Resorption ◽  
Bone Cells ◽  
Osteoclast Differentiation ◽  
Inhibitory Effect ◽  
Active Vitamin ◽  
Vitamin D Analogs ◽  
Active Vitamin D ◽  
Ckd Stage ◽  
Osteoclastic Differentiation

Abstract Background and Aims Active vitamin D analogs and calcimimetics are cornerstones for managing secondary hyperparathyroidism (SHPT) in chronic kidney disease (CKD). Their direct effects on bone cells remain to be determined. Method Peripheral blood mononuclear cells (PBMCs) of 19 pediatric CKD patients and 6 healthy donors (HD) were differentiated into osteoclasts in presence of M-CSF and RANKL. Effect of combined or single treatment with active vitamin D (1.25-D) and/or the calcimimetic KP2326 were evaluated onto osteoclast differentiation and osteoclast mediated bone resorption. Results 1.25-D inhibited osteoclastic differentiation, a significant resistance to 1.25-D was observed when CKD worsens. A significant albeit less important inhibitory effect of KP2326 on osteoclastic differentiation was also found both in cells derived from HD and CKD patients, through an activation of the Erk pathway. This inhibitory effect was not modified by CKD stage. Combinatorial treatment with 1.25-D and KP2326 did not result in synergistic effects. Last, KP2326 significantly inhibited human osteoclast-mediated bone resorption. Conclusion Both 1.25-D and KP2326 inhibit osteoclastic differentiation, however to a different extent. Whilst 1.25-D has no significant effect on bone resorption, KP2326 inhibits bone resorption. Recent data showed that calcimimetics also have a direct anabolic effect on bone, through the stimulation of osteoblastic differentiation and mineralization in human mesenchymal stem cells in vitro. All these results provide a strong rationale for a global positive effect of calcimimetics on bone remodeling. Calcimimetics also significantly decrease FGF23 levels. In the setting of global systematic deleterious effects of high FGF23 levels in CKD, and keeping in mind that active vitamin D analogs stimulate FGF 23 production, all these data could favor the use of decreased doses of 1.25-D with low-doses of calcimimetics in SHPT in dialysis, the combination of these two therapies already being proposed in the 2017 K-DIGO guidelines.

scholarly journals Effect of ED-71, a New Active Vitamin D Analog, on Bone Formation in an Orthopedically Expanded Suture in Rats. A Histomorphometric Study

2009 ◽  
Vol 03 (03) ◽  
pp. 165-172 ◽  
Author(s):  
Tancan Uysal ◽  
Mihri Amasyali ◽  
Sukru Enhos ◽  
Mehmet Fatih Sonmez ◽  
Deniz Sagdic
Keyword(s):  
Vitamin D ◽  
Bone Regeneration ◽  
Control Group ◽  
Maxillary Expansion ◽  
Active Vitamin ◽  
Positive Effects ◽  
Active Vitamin D ◽  
Vitamin D Analog ◽  
Experimental Group ◽  
Mid Palatal Suture

ABSTRACTObjectives: The aim of this experimental study was to evaluate the effects of ED-71, a new active vitamin D analog, on bone regeneration in response to expansion of the mid-palatal suture, in rats, histomorphometrically.Methods: Sixteen male 50-60 days old Wistar rats were separated into two equal groups (control and experimental). Both groups were subjected to expansion, and 30 grams of force was applied to the maxillary incisors with a helical-spring. Experimental group was treated with single-dose ED-71 (0.8 μg/kg body weight) in the mid-palatal suture locally and eight control animals received vehicle solution. Bone regeneration in the mid-palatal suture was evaluated by bone histomorphometric method and mineralized area (Md.Ar), fibrosis area (Fb.Ar), mineralized area/fibrosis area (Md.Ar/ Fb.Ar), bone area (B.Ar) and osteoblast number (N.Ob) parameters were evaluated. Mann Whitney-U test was used for statistical evaluation at P<.05 level.Results: Statistical analysis showed significant differences between groups for all investigated histomorphometric parameters. Md.Ar (P<.001), Md.Ar/Fb.Ar (P<.001), B.Ar (P<.01) and N.Ob (P<.001) parameters were significantly increased and Fb.Ar (P<.001) measurement was significantly decreased in experimental group. ED-71 group with a mean of 24.55±6.47 showed statistically higher N.Ob than the control group (mean N.Ob: 12.82±5.81).Conclusions: ED-71 has positive effects on early phase of bone regeneration in the mid-palatal suture in response to expansion and may be beneficial in routine maxillary expansion procedures. (Eur J Dent 2009;3:165-172)

Rationale for active vitamin D analog therapy in senile osteoporosis

1997 ◽  
Vol 60 (1) ◽  
pp. 100-105 ◽  
Author(s):  
K. Åkesson ◽  
K. -H. W. Lau ◽  
D. J. Baylink
Keyword(s):  
Vitamin D ◽  
Active Vitamin ◽  
Senile Osteoporosis ◽  
Active Vitamin D ◽  
Vitamin D Analog
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