Upregulation of calcitriol during pregnancy and skeletal recovery after lactation do not require parathyroid hormone

Kirby, Beth J.; Ma, Yue; Martin, Heather M.; Favaro, Kerri L Buckle; Karaplis, Andrew C.; Kovacs, Christopher S.

doi:10.1002/jbmr.1925

Cited by 71 publications

(82 citation statements)

References 120 publications

(181 reference statements)

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“…Moreover, there is no change in phosphate levels, and more reliable immunoassays, either immunoradiometry with the use of a double-antibody technique or electrochemiluminescence, confirm that the circulating PTH level slightly decreases during pregnancy and normalizes at the end of this state (18). Murine models further exclude the participation of the hormone in the increase in calcitriol level during pregnancy or the recovery of bone mass after lactation (19).…”

Section: Pth and Pthrpmentioning

confidence: 87%

ENDOCRINOLOGY IN PREGNANCY: Bone metabolic changes during pregnancy: a period of vulnerability to osteoporosis and fracture

Sanz-Salvador

Garcı́a-Pérez

Tarı́n

et al. 2015

European Journal of Endocrinology

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Changes in bone density and bone markers suggest that pregnancy is associated with deterioration of bone mass in the mother. The metabolism of calcium resets to allow for the needs imposed by the building of the fetal skeleton. The fetus contributes to the process through the output of regulators from the placenta. Understanding of the whole process is limited, but some changes are unambiguous. There is an increase in the circulating levels of vitamin D, but its functional impact is unclear. Fetal parathyroid hormone (PTH) and PTH-related peptide (PTHrp) play an indirect role through support of a calcium gradient that creates hypercalcemia in the fetus. Placental GH, which increases up to the end of pregnancy, may exert some anabolic effects, either directly or through the regulation of the IGF1 production. Other key regulators of bone metabolism, such as estrogens or prolactin, are elevated during pregnancy, but their role is uncertain. An increase in the ratio of receptor activator of nuclear factor kappa B ligand (RANKL) to osteoprotegerin (OPG) acts as an additional pro-resorbing factor in bone. The increase in bone resorption may lead to osteoporosis and fragility fracture, which have been diagnosed, although rarely. However, the condition is transitory as long-term studies do not link the number of pregnancies with osteoporosis. Prevention is limited by the lack of identifiable risk factors. When fractures are diagnosed, rest, analgesics, or, when indicated, orthopedic intervention have demonstrated efficacy. Systemic treatment with anti-osteoporotic drugs is effective, but the potential harm to the fetus imposes caution in their use.

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Section: Pth and Pthrpmentioning

confidence: 87%

ENDOCRINOLOGY IN PREGNANCY: Bone metabolic changes during pregnancy: a period of vulnerability to osteoporosis and fracture

Sanz-Salvador

Garcı́a-Pérez

Tarı́n

et al. 2015

European Journal of Endocrinology

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“…This results in fetal levels of 24-hydroxylated forms that are up to 40-fold higher than calcitriol in fetal rats and sheep (369,475,506). The high expression of Cyp24a1 in murine placentas is approximately equal to that of the maternal kidneys (310), confirming that the placenta has significant capacity to catabolize 25-hydroxyvitamin D and calcitriol into 24-hydroxylated forms.…”

Section: Calcitriolmentioning

confidence: 96%

“…These are also known as Hyp mice due to the hypophosphatemia Pth null Parathyroid hormone (PTH) (310,439,440,623) Pth/Cyp27b1 Double-mutant lacking PTH and calcitriol (747,749) Pth/Hoxa3 Double-mutant lacking both PTH and Hoxa3 (parathyroids)…”

Section: Protein(s) Encoded By the Genementioning

confidence: 99%

“…Normal peak bone density and skeletal calcium content differ markedly among mouse strains (48), with the commonly used inbred C57BL/6 strain having a significantly lower bone mass than the outbred Black Swiss strains (192,309,310,744). Serum and ionized calcium are also significantly lower in C57BL/6 compared with Black Swiss mice (340), but there are no obvious differences in calciotropic and phosphotropic hormone levels between the two strains.…”

Section: Animal Datamentioning

confidence: 99%

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Bone Development and Mineral Homeostasis in the Fetus and Neonate: Roles of the Calciotropic and Phosphotropic Hormones

Kovacs

2014

Physiological Reviews

211

188

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Mineral and bone metabolism are regulated differently in utero compared with the adult. The fetal kidneys, intestines, and skeleton are not dominant sources of mineral supply for the fetus. Instead, the placenta meets the fetal need for mineral by actively transporting calcium, phosphorus, and magnesium from the maternal circulation. These minerals are maintained in the fetal circulation at higher concentrations than in the mother and normal adult, and such high levels appear necessary for the developing skeleton to accrete a normal amount of mineral by term. Parathyroid hormone (PTH) and calcitriol circulate at low concentrations in the fetal circulation. Fetal bone development and the regulation of serum minerals are critically dependent on PTH and PTH-related protein, but not vitamin D/calcitriol, fibroblast growth factor-23, calcitonin, or the sex steroids. After birth, the serum calcium falls and phosphorus rises before gradually reaching adult values over the subsequent 24 -48 h. The intestines are the main source of mineral for the neonate, while the kidneys reabsorb mineral, and bone turnover contributes mineral to the circulation. This switch in the regulation of mineral homeostasis is triggered by loss of the placenta and a postnatal fall in serum calcium, and is followed in sequence by a rise in PTH and then an increase in calcitriol. Intestinal calcium absorption is initially a passive process facilitated by lactose, but later becomes active and calcitriol-dependent. However, calcitriol's role can be bypassed by increasing the calcium content of the diet, or by parenteral administration of calcium.

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“…FGF23 plasma levels are further modified by iron deficiency [25,26], pregnancy [27] and FGF23 secreting tumors [28].…”

Section: Introductionmentioning

confidence: 99%

NFκB-sensitive Orai1 expression in the regulation of FGF23 release

et al. 2015

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Fibroblast growth factor (FGF23) plasma levels are elevated in cardiac and renal failure and correlate with poor clinical prognosis of those disorders. Both disorders are associated with inflammation and activation of the inflammatory transcription factor NFB. An excessive FGF23 level is further observed in Klotho-deficient mice. The present study explored a putative sensitivity of FGF23 expression to transcription factor NFB, which is known to upregulate Orai1, the Ca(2+) channel accomplishing storeoperated Ca(2+) entry (SOCE). In osteoblastic cells (UMR106) and immortalized primary periosteal (IPO) cells, protein abundance was determined by Western blotting, and in UMR106 cells, transcript levels were quantified by RT-PCR, cytosolic Ca(2+) activity utilizing Fura-2-fluorescence, and SOCE from Ca(2+) entry following store depletion by thapsigargin. As a result, UMR106 and IPO cells expressed Ca(2+) channel Orai1. SOCE was lowered by NFB inhibitor wogonin as well as by Orai1 inhibitors 2-APB and YM58483. UMR106 cell Fgf23 transcripts were increased by stimulation of SOCE and Ca(2+) ionophore ionomycin and decreased by Orai inhibitors 2-APB, YM58483 and SKF96365, by Orai1 silencing, as well as by NFB inhibitors wogonin, withaferin A, and CAS 545380-34-5. In conclusion, Fgf23 expression is upregulated by stimulation of NFB-sensitive, store-operated Ca(2+) entry. KEY MES-SAGES Osteoblast UMR106 and IPO cells express Ca(2+) channel Orai1. Osteoblast store-operated Ca(2+) entry is accomplished by NFB-sensitive Orai1. Osteoblast Fgf23 transcription is upregulated by increase in the cytosolic Ca(2+) activity.

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Upregulation of calcitriol during pregnancy and skeletal recovery after lactation do not require parathyroid hormone

Cited by 71 publications

References 120 publications

ENDOCRINOLOGY IN PREGNANCY: Bone metabolic changes during pregnancy: a period of vulnerability to osteoporosis and fracture

ENDOCRINOLOGY IN PREGNANCY: Bone metabolic changes during pregnancy: a period of vulnerability to osteoporosis and fracture

Bone Development and Mineral Homeostasis in the Fetus and Neonate: Roles of the Calciotropic and Phosphotropic Hormones

NFκB-sensitive Orai1 expression in the regulation of FGF23 release

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