CYP24A1
1,25-dihydroxyvitamin D(3) 24-hydroxylase, mitochondrial precursor (EC 1.14.15.16) (24-OHase) (Vitamin D(3) 24-hydroxylase) (Cytochrome P450 24A1) (Cytochrome P450-CC24) [CYP24]
Publications[править]
To clarify the regulation of astragalus on the aging BMSCs model and the effect of astragalus on Vitamin D (VD)-FGF23-Klotho axis. siRNA was used to interfere the expression of VDR gene in aging BMSCs. Serum containing astragalus in different concentrations was added to the cultured cells. The expression of osteocalcin and alkaline phosphatase were detected by alizarin red staining and ELISA. Cell vitality was detected by flow cytometry, CCK-8 test, and [i]β[/i]-galactosidase staining. The expression of FGF23, Klotho, CYP27B1, and CYP24A1 was detected by qRT-PCR and western blot. The results showed that after reducing VDR gene expression, the aging BMSCs model showed decreased activity and osteogenic ability, increased expression of FGF23, Klotho and CYP24A1, and decreased expression of CYP27B1. After adding serum-containing astragalus, the activity of cells and the osteogenic ability was increased; the expression levels of FGF23, Klotho and CYP24A1 were decreased, the expression levels of CYP27B1 were increased, and the trend was more obvious with the increase of astragalus concentration. This study confirmed that astragalus could inhibit the aging of BMSCs and improve the osteogenesis ability by regulating the VD-FGF23-Klotho pathway. This study provided a certain research basis for the therapeutic of traditional Chinese medicine (TCM) on primary osteoporosis.
Keywords
- Astragalus
- BMSCs
- VD-FGF23-Klotho axis
- aging
- osteogenesis differentiation
Oleanolic acid (OA) is a triterpenoid with reported bone anti-resorption activities. The present study aimed to characterize its bone protective effects in vivo and to study its effects on vitamin D metabolism, both in vivo and in vitro. OA significantly increased bone mineral density, improved micro-architectural properties, reduced urinary Ca excretion, increased 1,25(OH)₂D₃ and renal CYP27B1 mRNA expression in mature C57BL/6 ovariectomised (OVX) mice. OA also improved bone properties, Ca balance, and exerted modulatory effects on renal CYP27B1 and CYP24A1 expressions in aged normal female Sprague-Dawley rats. In addition, OA significantly increased renal CYP27B1 mRNA and promoter activity, and suppressed CYP24A1 mRNA and protein expressions in human proximal tubule HKC-8 cells. OA exerted bone protective effects in mature OVX mice and aged female rats. This action on bone might be, at least in part, associated with its effects on Ca and vitamin D metabolism. The present findings suggest that OA is a potential drug candidate for the management of postmenopausal osteoporosis.
MeSH Terms
- 25-Hydroxyvitamin D3 1-alpha-Hydroxylase
- Animals
- Bone Density
- Bone Density Conservation Agents
- Bone Remodeling
- Bone and Bones
- Calcitriol
- Calcium
- Cell Line
- Disease Models, Animal
- Dose-Response Relationship, Drug
- Duodenum
- Female
- Humans
- Kidney Tubules, Proximal
- Mice, Inbred C57BL
- Oleanolic Acid
- Osteoporosis, Postmenopausal
- Ovariectomy
- Rats, Sprague-Dawley
- Vitamin D
- Vitamin D3 24-Hydroxylase
- X-Ray Microtomography
Keywords
- aging
- calcium
- oleanolic acid
- osteoporosis
- ovariectomised
- vitamin D
Despite the high prevalence of vitamin D deficiency among older adults in the UK, studies investigating the determinants of vitamin D status in this group are lacking. We conducted a cross-sectional study in 222 older adults living in sheltered accommodation in London, UK, who were screened for participation in a clinical trial of vitamin D supplementation for the prevention of acute respiratory infection. Details of potential demographic and lifestyle determinants of vitamin D status were collected by questionnaire and blood samples were taken for analysis of serum 25-hydroxyvitamin D (25[OH]D) concentration and DNA extraction. Fifteen single nucleotide polymorphisms (SNP) in 6 genes (DBP, DHCR7, CYP2R1, CYP27B1, CYP24A1, VDR) previously reported to associate with circulating 25(OH)D concentration were typed using Taqman allelic discrimination assays. Linear regression was used to identify environmental and genetic factors independently associated with serum 25(OH)D concentration. Mean serum 25(OH)D concentration was 42.7nmol/L (SD 22.0); 144/222 (64.9%) participants had serum 25(OH)D concentrations <50nmol/L. The following factors were independently associated with lower serum 25(OH)D concentration: non-white ethnicity (-8.6nmol/L, 95% CI -14.9 to -2.3, P=0.008); lack of vitamin D supplement consumption (-17.1nmol/L, 95% CI -23.3 to -10.9, P<0.001) vs. taking a daily supplement; sampling in Q1/January-March (-12.2nmol/L, 95% CI -21.5 to -2.9, P=0.01), and sampling in Q4/October-December (-10.3nmol/L, 95% CI -20.2 to -0.4, P=0.04) vs. sampling in Q3/July-September. None of the 15 SNP investigated independently associated with serum 25(OH)D concentration after correcting for multiple comparisons. In conclusion, vitamin D deficiency was highly prevalent among the older adults in this study; non-White ethnicity, lack of vitamin D supplement consumption and sampling in winter and spring independently associated with lower vitamin D status.
MeSH Terms
- 25-Hydroxyvitamin D3 1-alpha-Hydroxylase
- Aged
- Aged, 80 and over
- Aging
- Cholestanetriol 26-Monooxygenase
- Clinical Trials as Topic
- Cohort Studies
- Cross-Sectional Studies
- Cytochrome P450 Family 2
- DNA-Binding Proteins
- Diet
- Dietary Supplements
- Female
- Genetic Predisposition to Disease
- Humans
- London
- Male
- Middle Aged
- Oxidoreductases Acting on CH-CH Group Donors
- Polymorphism, Single Nucleotide
- Receptors, Calcitriol
- Seasons
- Transcription Factors
- Vitamin D
- Vitamin D Deficiency
- Vitamin D3 24-Hydroxylase
Keywords
- Ageing
- Diet
- Polymorphism
- Season
- Single nucleotide
- Vitamin D
The nuclear vitamin D receptor (VDR) binds 1,25-dihydroxyvitamin D3 (1,25D), its high affinity renal endocrine ligand, to signal intestinal calcium and phosphate absorption plus bone remodeling, generating a mineralized skeleton free of rickets/osteomalacia with a reduced risk of osteoporotic fractures. 1,25D/VDR signaling regulates the expression of TRPV6, BGP, SPP1, LRP5, RANKL and OPG, while achieving feedback control of mineral ions to prevent age-related ectopic calcification by governing CYP24A1, PTH, FGF23, PHEX, and klotho transcription. Vitamin D also elicits numerous intracrine actions when circulating 25-hydroxyvitamin D3, the metabolite reflecting vitamin D status, is converted to 1,25D locally by extrarenal CYP27B1, and binds VDR to promote immunoregulation, antimicrobial defense, xenobiotic detoxification, anti-inflammatory/anticancer actions and cardiovascular benefits. VDR also affects Wnt signaling through direct interaction with beta-catenin, ligand-dependently blunting beta-catenin mediated transcription in colon cancer cells to attenuate growth, while potentiating beta-catenin signaling via VDR ligand-independent mechanisms in osteoblasts and keratinocytes to function osteogenically and as a pro-hair cycling receptor, respectively. Finally, VDR also drives the mammalian hair cycle in conjunction with the hairless corepressor by repressing SOSTDC1, S100A8/S100A9, and PTHrP. Hair provides a shield against UV-induced skin damage and cancer in terrestrial mammals, illuminating another function of VDR that facilitates healthful aging.
MeSH Terms
- Aging
- Animals
- Calcium
- Cell Nucleus
- Gene Expression Regulation
- Humans
- Keratinocytes
- Mice
- Models, Biological
- Osteopontin
- Phosphates
- Receptors, Calcitriol
- Signal Transduction
- Wnt Proteins
- beta Catenin