| 20200995 |
Weber K, Zeitz U, Bergow C, Hirmer S, Schuler C, Erben RG: Vitamin D Independent Therapeutic Effects of Extracellular Calcium in a Mouse Model of Adult-Onset Secondary Hyperparathyroidism. J Bone Miner Res. 2009 Dec 14:1-41.
Cell proliferation and parathyroid hormone secretion in the parathyroid gland are known to be regulated by vitamin D and by extracellular calcium. Here, we examined the vitamin D independent effects of correction of extracellular calcium in an adult-onset secondary hyperparathyroidism (sHPT) model, using mice with a nonfunctioning vitamin D receptor (VDR). Wild-type and homozygous VDR mutant mice were kept on a rescue diet (RD) containing 2% calcium (Ca), 1.25% phosphorus (P), and 20% lactose until they were 4 months or 1 year of age. Subsequently, 4-month-old mice were switched to a challenge diet (CD) containing 0.5% Ca, 0.4% P, and 0% lactose. After 2 months on CD, groups of VDR mutant mice were either fed CD, a normal mouse chow with 0.9% Ca, 0.7% P, and 0% lactose, or RD for another 3 months. Feeding RD protected VDR mutants against sHPT over 1 year, showing that vitamin D is not essential for long-term control of the function and proliferation of parathyroid cells. When 4-month-old VDR mutants were switched from RD to CD for 2 months, they developed severe sHPT associated with hypertrophy and hyperplasia of parathyroid glands and profound bone loss. Subsequent feeding of the RD during a 3-month therapy phase fully corrected sHPT, reduced chief cell proliferation, and reduced maximum parathyroid gland area by 25% by cell atrophy. There was no evidence of RD-induced chief cell apoptosis. We conclude that signaling via the calcium-sensing receptor regulates chief cell function and size in the absence of signaling through the VDR. |
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