Skip to main content
Erschienen in: Calcified Tissue International 5/2015

01.05.2015 | Original Research

The Generation of C-3α Epimer of 25-Hydroxyvitamin D and Its Biological Effects on Bone Mineral Density in Adult Rodents

verfasst von: Christina Bianchini, Paula Lavery, Sherry Agellon, Hope A. Weiler

Erschienen in: Calcified Tissue International | Ausgabe 5/2015

Einloggen, um Zugang zu erhalten

Abstract

The source and function of C-3α epimer of 25(OH)D (C-3 epimer) is unknown. The objectives were to (1) establish if increasing doses of vitamin D (VD) results in a proportionate dose–response in C-3 epimer; and (2) determine the biological response of bone to C-3 epimer treatment. Sprague Dawley rats (12 weeks, n = 36 female, n = 36 male) were randomized to control AIN93-M diet (1 IU VD3/g diet) or an experimental diet for 8 weeks containing VD3 at 2 or 4 IU/g diet, C-3 epimer at 0.5 or 1 IU/g diet or 25(OH)D (0.5 IU/g diet). BW and food consumption were measured weekly. Blood was sampled at week 0, 4, and 8 for assessment of VD metabolites and bone metabolism biomarkers. DXA (week 0, 4, and 8) and in vivo micro CT (μCT) (week 0 and 8) were performed in vivo plus ex vivo μCT imaging and bone biomechanics. Dietary intake and anthropometry did not differ among diet groups. The dose–response of VD generated significantly elevated C-3 epimer only in females with concentrations of 4 IU VD diet group [mean 84.6 (62.5) nmol/L] exceeding control [mean 21.4 (18.5) nmol/L, p = 0.005]. Both sexes in the 25(OH)D group did not show significant increases in C-3 epimer, whereas 0.5 and 1 IU epimer groups exceeded 100 nmol/L of C-3 epimer by 8 weeks. These data suggest C-3 epimer is endogenously generated with higher intakes of VD. Endogenous and exogenous C-3 epimer accumulates in serum without impact upon bone health outcomes in a healthy young adult model over 8 weeks.
Anhänge
Nur mit Berechtigung zugänglich
Literatur
1.
Zurück zum Zitat Bailey D, Veljkovic K, Yazdanpanah M, Adeli K (2013) Analytical measurement and clinical relevance of vitamin D(3) C3-epimer. Clin Biochem 46(3):190–196CrossRefPubMed Bailey D, Veljkovic K, Yazdanpanah M, Adeli K (2013) Analytical measurement and clinical relevance of vitamin D(3) C3-epimer. Clin Biochem 46(3):190–196CrossRefPubMed
2.
Zurück zum Zitat Genazzani AR, Palumbo MA, de Micheroux AA, Artini PG, Criscuolo M, Ficarra G, Guo A-L, Benelli A, Bertolini A, Petraglia F (1995) Evidence for a role for the neurosteroid allopregnanolone in the modulation of reproductive function in female rats. Eur J Endocrinol 133(3):375–380CrossRefPubMed Genazzani AR, Palumbo MA, de Micheroux AA, Artini PG, Criscuolo M, Ficarra G, Guo A-L, Benelli A, Bertolini A, Petraglia F (1995) Evidence for a role for the neurosteroid allopregnanolone in the modulation of reproductive function in female rats. Eur J Endocrinol 133(3):375–380CrossRefPubMed
3.
Zurück zum Zitat Reddy GS, Muralidharan KR, Okamura WH, Tserng KY, McLane JA (2001) Metabolism of 1alpha,25-dihydroxyvitamin D(3) and its C-3 epimer 1alpha,25-dihydroxy-3-epi-vitamin D(3) in neonatal human keratinocytes. Steroids 66(3–5):441–450CrossRefPubMed Reddy GS, Muralidharan KR, Okamura WH, Tserng KY, McLane JA (2001) Metabolism of 1alpha,25-dihydroxyvitamin D(3) and its C-3 epimer 1alpha,25-dihydroxy-3-epi-vitamin D(3) in neonatal human keratinocytes. Steroids 66(3–5):441–450CrossRefPubMed
4.
Zurück zum Zitat Kamao M, Hatakeyama S, Sakaki T, Sawada N, Inouye K, Kubodera N, Reddy GS, Okano T (2005) Measurement and characterization of C-3 epimerization activity toward vitamin D3. Arch Biochem Biophys 436(1):196–205CrossRefPubMed Kamao M, Hatakeyama S, Sakaki T, Sawada N, Inouye K, Kubodera N, Reddy GS, Okano T (2005) Measurement and characterization of C-3 epimerization activity toward vitamin D3. Arch Biochem Biophys 436(1):196–205CrossRefPubMed
5.
Zurück zum Zitat Fleet JC, Bradley J, Reddy GS, Ray R, Wood RJ (1996) 1 alpha,25-(OH)2-vitamin D3 analogs with minimal in vivo calcemic activity can stimulate significant transepithelial calcium transport and mRNA expression in vitro. Arch Biochem Biophys 329(2):228–234CrossRefPubMed Fleet JC, Bradley J, Reddy GS, Ray R, Wood RJ (1996) 1 alpha,25-(OH)2-vitamin D3 analogs with minimal in vivo calcemic activity can stimulate significant transepithelial calcium transport and mRNA expression in vitro. Arch Biochem Biophys 329(2):228–234CrossRefPubMed
6.
Zurück zum Zitat Kamao M, Tatematsu S, Hatakeyama S, Sakaki T, Sawada N, Inouye K, Ozono K, Kubodera N, Reddy GS, Okano T (2004) C-3 epimerization of vitamin D3 metabolites and further metabolism of C-3 epimers: 25-hydroxyvitamin D3 is metabolized to 3-epi-25-hydroxyvitamin D3 and subsequently metabolized through C-1alpha or C-24 hydroxylation. J Biol Chem 279(16):15897–15907CrossRefPubMed Kamao M, Tatematsu S, Hatakeyama S, Sakaki T, Sawada N, Inouye K, Ozono K, Kubodera N, Reddy GS, Okano T (2004) C-3 epimerization of vitamin D3 metabolites and further metabolism of C-3 epimers: 25-hydroxyvitamin D3 is metabolized to 3-epi-25-hydroxyvitamin D3 and subsequently metabolized through C-1alpha or C-24 hydroxylation. J Biol Chem 279(16):15897–15907CrossRefPubMed
7.
Zurück zum Zitat Rehan VK, Torday JS, Peleg S, Gennaro L, Vouros P, Padbury J, Rao DS, Reddy GS (2002) 1Alpha,25-dihydroxy-3-epi-vitamin D3, a natural metabolite of 1alpha,25-dihydroxy vitamin D3: production and biological activity studies in pulmonary alveolar type II cells. Mol Genet Metab 76(1):46–56CrossRefPubMed Rehan VK, Torday JS, Peleg S, Gennaro L, Vouros P, Padbury J, Rao DS, Reddy GS (2002) 1Alpha,25-dihydroxy-3-epi-vitamin D3, a natural metabolite of 1alpha,25-dihydroxy vitamin D3: production and biological activity studies in pulmonary alveolar type II cells. Mol Genet Metab 76(1):46–56CrossRefPubMed
8.
Zurück zum Zitat Rhieu SY, Annalora AJ, Wang G, Flarakos CC, Gathungu RM, Vouros P, Sigueiro R, Mourino A, Schuster I, Palmore GT, Reddy GS (2013) Metabolic stability of 3-Epi-1alpha,25-dihydroxyvitamin D3 over 1 alpha 25-dihydroxyvitamin D3: metabolism and molecular docking studies using rat CYP24A1. J Cell Biochem 114(10):2293–2305CrossRefPubMed Rhieu SY, Annalora AJ, Wang G, Flarakos CC, Gathungu RM, Vouros P, Sigueiro R, Mourino A, Schuster I, Palmore GT, Reddy GS (2013) Metabolic stability of 3-Epi-1alpha,25-dihydroxyvitamin D3 over 1 alpha 25-dihydroxyvitamin D3: metabolism and molecular docking studies using rat CYP24A1. J Cell Biochem 114(10):2293–2305CrossRefPubMed
9.
Zurück zum Zitat Gallo S, Comeau K, Vanstone C, Agellon S, Sharma A, Jones G, L’Abbe M, Khamessan A, Rodd C, Weiler H (2013) Effect of different dosages of oral vitamin D supplementation on vitamin D status in healthy, breastfed infants: a randomized trial. JAMA 309(17):1785–1792CrossRefPubMed Gallo S, Comeau K, Vanstone C, Agellon S, Sharma A, Jones G, L’Abbe M, Khamessan A, Rodd C, Weiler H (2013) Effect of different dosages of oral vitamin D supplementation on vitamin D status in healthy, breastfed infants: a randomized trial. JAMA 309(17):1785–1792CrossRefPubMed
10.
Zurück zum Zitat Anderson PH, Sawyer RK, Moore AJ, May BK, O’Loughlin PD, Morris HA (2008) Vitamin D depletion induces RANKL-mediated osteoclastogenesis and bone loss in a rodent model. J Bone Miner Res 23(11):1789–1797CrossRefPubMed Anderson PH, Sawyer RK, Moore AJ, May BK, O’Loughlin PD, Morris HA (2008) Vitamin D depletion induces RANKL-mediated osteoclastogenesis and bone loss in a rodent model. J Bone Miner Res 23(11):1789–1797CrossRefPubMed
11.
Zurück zum Zitat Lee AM, Anderson PH, Sawyer RK, Moore AJ, Forwood MR, Steck R, Morris HA, O’Loughlin PD (2010) Discordant effects of vitamin D deficiency in trabecular and cortical bone architecture and strength in growing rodents. J Steroid Biochem Mol Biol 121(1–2):284–287CrossRefPubMed Lee AM, Anderson PH, Sawyer RK, Moore AJ, Forwood MR, Steck R, Morris HA, O’Loughlin PD (2010) Discordant effects of vitamin D deficiency in trabecular and cortical bone architecture and strength in growing rodents. J Steroid Biochem Mol Biol 121(1–2):284–287CrossRefPubMed
12.
Zurück zum Zitat Fleet JC, Gliniak C, Zhang Z, Xue Y, Smith KB, McCreedy R, Adedokun SA (2008) Serum metabolite profiles and target tissue gene expression define the effect of cholecalciferol intake on calcium metabolism in rats and mice. J Nutr 138(6):1114–1120PubMedCentralPubMed Fleet JC, Gliniak C, Zhang Z, Xue Y, Smith KB, McCreedy R, Adedokun SA (2008) Serum metabolite profiles and target tissue gene expression define the effect of cholecalciferol intake on calcium metabolism in rats and mice. J Nutr 138(6):1114–1120PubMedCentralPubMed
13.
Zurück zum Zitat Pye KM, Wakefield AP, Aukema HM, House JD, Ogborn MR, Weiler HA (2009) A high mixed protein diet reduces body fat without altering the mechanical properties of bone in female rats. J Nutr 139(11):2099–2105CrossRefPubMed Pye KM, Wakefield AP, Aukema HM, House JD, Ogborn MR, Weiler HA (2009) A high mixed protein diet reduces body fat without altering the mechanical properties of bone in female rats. J Nutr 139(11):2099–2105CrossRefPubMed
14.
Zurück zum Zitat Reeves PG, Nielsen FH, Fahey GC Jr (1993) AIN-93 purified diets for laboratory rodents: final report of the American Institute of Nutrition ad hoc writing committee on the reformulation of the AIN-76A rodent diet. J Nutr 123(11):1939–1951PubMed Reeves PG, Nielsen FH, Fahey GC Jr (1993) AIN-93 purified diets for laboratory rodents: final report of the American Institute of Nutrition ad hoc writing committee on the reformulation of the AIN-76A rodent diet. J Nutr 123(11):1939–1951PubMed
15.
Zurück zum Zitat Brouwers JE, Van Rietbergen B, Huiskes R (2007) No effects of in vivo micro-CT radiation on structural parameters and bone marrow cells in proximal tibia of wistar rats detected after eight weekly scans. J Orthop Res 25(10):1325–1332CrossRefPubMed Brouwers JE, Van Rietbergen B, Huiskes R (2007) No effects of in vivo micro-CT radiation on structural parameters and bone marrow cells in proximal tibia of wistar rats detected after eight weekly scans. J Orthop Res 25(10):1325–1332CrossRefPubMed
16.
Zurück zum Zitat Meganck JA, Kozloff KM, Thornton MM, Broski SM, Goldstein SA (2009) Beam hardening artifacts in micro-computed tomography scanning can be reduced by X-ray beam filtration and the resulting images can be used to accurately measure BMD. Bone 45(6):1104–1116CrossRefPubMedCentralPubMed Meganck JA, Kozloff KM, Thornton MM, Broski SM, Goldstein SA (2009) Beam hardening artifacts in micro-computed tomography scanning can be reduced by X-ray beam filtration and the resulting images can be used to accurately measure BMD. Bone 45(6):1104–1116CrossRefPubMedCentralPubMed
17.
Zurück zum Zitat Crenshaw TD, Peo ER, Lewis AJ, Moser BD (1981) Bone strength as a trait for assessing mineralization in swine: a critical review of techniques involved. J Anim Sci 53(3):827–835 Crenshaw TD, Peo ER, Lewis AJ, Moser BD (1981) Bone strength as a trait for assessing mineralization in swine: a critical review of techniques involved. J Anim Sci 53(3):827–835
18.
Zurück zum Zitat Brown AJ, Ritter CS, Weiskopf AS, Vouros P, Sasso GJ, Uskokovic MR, Wang G, Reddy GS (2005) Isolation and identification of 1alpha-hydroxy-3-epi-vitamin D3, a potent suppressor of parathyroid hormone secretion. J Cell Biochem 96(3):569–578CrossRefPubMed Brown AJ, Ritter CS, Weiskopf AS, Vouros P, Sasso GJ, Uskokovic MR, Wang G, Reddy GS (2005) Isolation and identification of 1alpha-hydroxy-3-epi-vitamin D3, a potent suppressor of parathyroid hormone secretion. J Cell Biochem 96(3):569–578CrossRefPubMed
19.
Zurück zum Zitat Lensmeyer G, Poquette M, Wiebe D, Binkley N (2012) The C-3 epimer of 25-hydroxyvitamin D(3) is present in adult serum. J Clin Endocrinol Metabol 97(1):163–168CrossRef Lensmeyer G, Poquette M, Wiebe D, Binkley N (2012) The C-3 epimer of 25-hydroxyvitamin D(3) is present in adult serum. J Clin Endocrinol Metabol 97(1):163–168CrossRef
20.
Zurück zum Zitat Schleicher RL, Encisco SE, Chaudhary-Webb M, Paliakov E, McCoy LF, Pfeiffer CM (2011) Isotope dilution ultra performance liquid chromatography-tandem mass spectrometry method for simultaneous measurement of 25-hydroxyvitamin D2, 25-hydroxyvitamin D3 and 3-epi-25-hydroxyvitamin D3 in human serum. Clin Chim Acta 412(17–18):1594–1599CrossRefPubMed Schleicher RL, Encisco SE, Chaudhary-Webb M, Paliakov E, McCoy LF, Pfeiffer CM (2011) Isotope dilution ultra performance liquid chromatography-tandem mass spectrometry method for simultaneous measurement of 25-hydroxyvitamin D2, 25-hydroxyvitamin D3 and 3-epi-25-hydroxyvitamin D3 in human serum. Clin Chim Acta 412(17–18):1594–1599CrossRefPubMed
21.
Zurück zum Zitat Yazdanpanah M, Bailey D, Walsh W, Wan B, Adeli K (2013) Analytical measurement of serum 25-OH-vitamin D(3), 25-OH-vitamin D(2) and their C3-epimers by LC-MS/MS in infant and pediatric specimens. Clin Biochem 46(13–14):1264–1271CrossRefPubMed Yazdanpanah M, Bailey D, Walsh W, Wan B, Adeli K (2013) Analytical measurement of serum 25-OH-vitamin D(3), 25-OH-vitamin D(2) and their C3-epimers by LC-MS/MS in infant and pediatric specimens. Clin Biochem 46(13–14):1264–1271CrossRefPubMed
22.
Zurück zum Zitat Engelman CD, Bo R, Zuelsdorff M, Steltenpohl H, Kirby T, Nieto FJ (2014) Epidemiologic study of the C-3 epimer of 25-hydroxyvitamin D(3) in a population-based sample. Clin Nutr 33(3):421–425CrossRefPubMed Engelman CD, Bo R, Zuelsdorff M, Steltenpohl H, Kirby T, Nieto FJ (2014) Epidemiologic study of the C-3 epimer of 25-hydroxyvitamin D(3) in a population-based sample. Clin Nutr 33(3):421–425CrossRefPubMed
23.
Zurück zum Zitat Lensmeyer G, Poquette M, Wiebe D, Binkley N (2011) The C-3 epimer of 25-hydroxyvitamin D3 is present in adult serum. J Clin Endocrinol Metabol 97(1):163–168CrossRef Lensmeyer G, Poquette M, Wiebe D, Binkley N (2011) The C-3 epimer of 25-hydroxyvitamin D3 is present in adult serum. J Clin Endocrinol Metabol 97(1):163–168CrossRef
24.
Zurück zum Zitat Witschi AK, Liesegang A, Gebert S, Weber GM, Wenk C (2011) Effect of source and quantity of dietary vitamin D in maternal and creep diets on bone metabolism and growth in piglets. J Anim Sci 89(6):1844–1852CrossRefPubMed Witschi AK, Liesegang A, Gebert S, Weber GM, Wenk C (2011) Effect of source and quantity of dietary vitamin D in maternal and creep diets on bone metabolism and growth in piglets. J Anim Sci 89(6):1844–1852CrossRefPubMed
25.
Zurück zum Zitat Rhieu SY, Annalora AJ, Wang G, Flarakos CC, Gathungu RM, Vouros P, Sigueiro R, Mourino A, Schuster I, Palmore GT, Reddy GS (2013) Metabolic stability of 3-epi-1alpha,25-dihydroxyvitamin D3 over 1 alpha 25-dihydroxyvitamin D3: metabolism and molecular docking studies using rat CYP24A1. J Cell Biochem 114(10):2293–2305CrossRefPubMed Rhieu SY, Annalora AJ, Wang G, Flarakos CC, Gathungu RM, Vouros P, Sigueiro R, Mourino A, Schuster I, Palmore GT, Reddy GS (2013) Metabolic stability of 3-epi-1alpha,25-dihydroxyvitamin D3 over 1 alpha 25-dihydroxyvitamin D3: metabolism and molecular docking studies using rat CYP24A1. J Cell Biochem 114(10):2293–2305CrossRefPubMed
26.
Zurück zum Zitat Masuda S, Kamao M, Schroeder NJ, Makin HL, Jones G, Kremer R, Rhim J, Okano T (2000) Characterization of 3-epi-1alpha,25-dihydroxyvitamin D3 involved in 1alpha,25-dihydroxyvitamin D3 metabolic pathway in cultured cell lines. Biol Pharm Bull 23(2):133–139CrossRefPubMed Masuda S, Kamao M, Schroeder NJ, Makin HL, Jones G, Kremer R, Rhim J, Okano T (2000) Characterization of 3-epi-1alpha,25-dihydroxyvitamin D3 involved in 1alpha,25-dihydroxyvitamin D3 metabolic pathway in cultured cell lines. Biol Pharm Bull 23(2):133–139CrossRefPubMed
27.
Zurück zum Zitat Gallo S, Comeau K, Agellon S, Vanstone C, Sharma A, Jones G, L’Abbe M, Khamessan A, Weiler H, Rodd C (2014) Methodological issues in assessing plasma 25-hydroxyvitamin D concentration in newborn infants. Bone 61:186–190CrossRefPubMed Gallo S, Comeau K, Agellon S, Vanstone C, Sharma A, Jones G, L’Abbe M, Khamessan A, Weiler H, Rodd C (2014) Methodological issues in assessing plasma 25-hydroxyvitamin D concentration in newborn infants. Bone 61:186–190CrossRefPubMed
28.
Zurück zum Zitat Olfert ED, Cross BM, McWilliam AA (1993) Guide to the care and use of experimental animals, vol 2. Canadian Council on Animal Care, Ottawa Olfert ED, Cross BM, McWilliam AA (1993) Guide to the care and use of experimental animals, vol 2. Canadian Council on Animal Care, Ottawa
Metadaten
Titel
The Generation of C-3α Epimer of 25-Hydroxyvitamin D and Its Biological Effects on Bone Mineral Density in Adult Rodents
verfasst von
Christina Bianchini
Paula Lavery
Sherry Agellon
Hope A. Weiler
Publikationsdatum
01.05.2015
Verlag
Springer US
Erschienen in
Calcified Tissue International / Ausgabe 5/2015
Print ISSN: 0171-967X
Elektronische ISSN: 1432-0827
DOI
https://doi.org/10.1007/s00223-015-9973-9

Weitere Artikel der Ausgabe 5/2015

Calcified Tissue International 5/2015 Zur Ausgabe

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.