Stimulatory effects of phenytoin on osteoblastic differentiation of fetal rat calvaria cells in culture

Ikedo, Dai; Ohishi, Keiji; Yamauchi, Noriyuki; Kataoka, Masatoshi; Kido, Jun‐ichi; Nagata, Toshihiko

doi:10.1016/s8756-3282(99)00222-7

Cited by 25 publications

(22 citation statements)

References 41 publications

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“…Osteoblastic differentiation was demonstrated by the appearance of bone nodules (von Kossa staining), strong APase activity, and bone-specific osteocalcin gene expression. [23][24][25][26] High levels of APase in F-treated cultures were confirmed by histochemical (Fig. 3) and enzyme assay methods (Table I).…”

Section: Discussionmentioning

confidence: 64%

“…Among the noncollagenous proteins produced by osteoblasts, osteocalcin is the most abundant bone matrix protein, is synthesized particularly by osteoblasts, [23][24][25] and is a marker for the identification of tissue as bone. [23][24][25][26] In the present experiment, total RNA was extracted from mineralized nodules produced by MSCs and the mRNA level of osteocalcin was analyzed. Strong transcription of this gene was found in FK506-treated MSCs by Northern blot analysis, similar to that in Dex-treated cultures.…”

Section: Discussionmentioning

confidence: 99%

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Stimulation of osteogenic activity in mesenchymal stem cells by FK506

Dai

Dong

Fang

et al. 2007

J Biomedical Materials Res

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The aim of this study was to investigate the osteogenic induction by tacrolimus hydrate (FK506) of rat bone marrow-derived mesenchymal stem cells (MSCs). MSCs were cultured in alpha-MEM containing either (1) L-ascorbic acid-2-phosphate (AsAP) and beta-glycerophosphate (beta-GP) as a control; (2) AsAP and beta-GP plus FK506; (3) AsAP and beta-GP plus Dex; or (4) AsAP and beta-GP plus FK506 and Dex. The concentration of FK506 was varied from 5 to 5000 nM to investigate the dose-effect relationship. Sixteen days later, cells were harvested for analysis. Examination of morphology, alkaline phosphatase (APase) activity, calcium deposition, bone nodule formation, osteocalcin mRNA expression, and mineralized extracellular matrix formation showed that the osteogenic differentiation of MSCs was greatly promoted, bone nodule formation was enhanced, APase activity and the expression of osteocalcin mRNA were increased. FK506 was much more effective when combined with Dex. The best results were achieved with alpha-MEM containing 0.25 mM AsAP, 10 mM beta-GP, 10 nM Dex, and 50 nM FK506. Formation of bone in vivo was also studied by transplanting MSCs-loaded ceramic cubes subcutaneously into the back of rats. Satisfactory results were achieved at 4 and 8 weeks. FK506 should be considered for use as an osteogenic agent.

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Section: Discussionmentioning

confidence: 64%

Section: Discussionmentioning

confidence: 99%

Stimulation of osteogenic activity in mesenchymal stem cells by FK506

Dai

Dong

Fang

et al. 2007

J Biomedical Materials Res

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“…16,17,19 The number of BN stained as dark dots was determined using computer software. 16,17,19 The number of BN stained as dark dots was determined using computer software.…”

Section: Determination Of Bone Nodule (Bn) Numbermentioning

confidence: 99%

Substance P Enhances the Inhibition of Osteoblastic Cell Differentiation Induced by Lipopolysaccharide From Porphyromonas gingivalis

Azuma

Kido

Ikedo

et al. 2004

Journal of Periodontology

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“…PT might induce a substantial number of fractures and consequential costs [42] in vivo and in vitro [77,78]. PT may also induce the expression of CYP450, which increases the degradation of bioavailable vitamin D, decreases absorption of calcium in the gut, decreases serum levels of calcium and phosphate, and increases PTH.…”

Section: Introductionmentioning

confidence: 99%

The Impact of Anti-Epileptic Drugs on Growth and Bone Metabolism

Fan

Lee

Chang

et al. 2016

IJMS

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Epilepsy is a common neurological disorder worldwide and anti-epileptic drugs (AEDs) are always the first choice for treatment. However, more than 50% of patients with epilepsy who take AEDs have reported bone abnormalities. Cytochrome P450 (CYP450) isoenzymes are induced by AEDs, especially the classical AEDs, such as benzodiazepines (BZDs), carbamazepine (CBZ), phenytoin (PT), phenobarbital (PB), and valproic acid (VPA). The induction of CYP450 isoenzymes may cause vitamin D deficiency, hypocalcemia, increased fracture risks, and altered bone turnover, leading to impaired bone mineral density (BMD). Newer AEDs, such as levetiracetam (LEV), oxcarbazepine (OXC), lamotrigine (LTG), topiramate (TPM), gabapentin (GP), and vigabatrin (VB) have broader spectra, and are safer and better tolerated than the classical AEDs. The effects of AEDs on bone health are controversial. This review focuses on the impact of AEDs on growth and bone metabolism and emphasizes the need for caution and timely withdrawal of these medications to avoid serious disabilities.

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Stimulatory effects of phenytoin on osteoblastic differentiation of fetal rat calvaria cells in culture

Cited by 25 publications

References 41 publications

Stimulation of osteogenic activity in mesenchymal stem cells by FK506

Stimulation of osteogenic activity in mesenchymal stem cells by FK506

Substance P Enhances the Inhibition of Osteoblastic Cell Differentiation Induced by Lipopolysaccharide From Porphyromonas gingivalis

The Impact of Anti-Epileptic Drugs on Growth and Bone Metabolism

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