Bone Structure and Metabolism in Calcium-Deficient Rats

Harrison, Mike T.; Fraser, Russell

doi:10.1677/joe.0.0210197

Cited by 106 publications

(21 citation statements)

References 5 publications

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“…Indeed, only when increased 1,25(OH) 2 D levels could elicit a skeletal response [i.e., in Vdr int-mice, 1,25(OH) 2 Dtreated Vdr oc+ mice, and Vdr int+ mice receiving a low-calcium diet, but not in Vdr -/-or Vdr oc-mice] was bone matrix mineralization inhibited, and was a profound shift of calcium from bone to serum observed. In agreement with this finding, bone fractures that are associated with dietary calcium restriction in growing rats are prevented when the low-calcium diet is combined with vitamin D deficiency, but the latter condition is associated with more pronounced hypocalcemia (4). Several lines of evidence support our finding that increased 1,25(OH) 2 D serum levels suppresses bone matrix mineralization.…”

Section: Discussionsupporting

confidence: 89%

“…The action of 1,25(OH) 2 D therefore seems to be important in the normal skeletal responses that prevent hypocalcemia during a negative calcium balance. Previous dietary studies have shown that the amount of calcium stored in bone declines when dietary calcium supply is insufficient (4). However, the molecular skeletal adaptations that redirect calcium from bone to serum are still not identified.…”

Section: Introductionmentioning

confidence: 99%

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Normocalcemia is maintained in mice under conditions of calcium malabsorption by vitamin D–induced inhibition of bone mineralization

et al. 2012

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Serum calcium levels are tightly controlled by an integrated hormone-controlled system that involves active vitamin D [1,25(OH) 2 D], which can elicit calcium mobilization from bone when intestinal calcium absorption is decreased. The skeletal adaptations, however, are still poorly characterized. To gain insight into these issues, we analyzed the consequences of specific vitamin D receptor (Vdr) inactivation in the intestine and in mature osteoblasts on calcium and bone homeostasis. We report here that decreased intestinal calcium absorption in intestine-specific Vdr knockout mice resulted in severely reduced skeletal calcium levels so as to ensure normal levels of calcium in the serum. Furthermore, increased 1,25(OH) 2 D levels not only stimulated bone turnover, leading to osteopenia, but also suppressed bone matrix mineralization. This resulted in extensive hyperosteoidosis, also surrounding the osteocytes, and hypomineralization of the entire bone cortex, which may have contributed to the increase in bone fractures. Mechanistically, osteoblastic VDR signaling suppressed calcium incorporation in bone by directly stimulating the transcription of genes encoding mineralization inhibitors. Ablation of skeletal Vdr signaling precluded this calcium transfer from bone to serum, leading to better preservation of bone mass and mineralization. These findings indicate that in mice, maintaining normocalcemia has priority over skeletal integrity, and that to minimize skeletal calcium storage, 1,25(OH) 2 D not only increases calcium release from bone, but also inhibits calcium incorporation in bone. IntroductionIonized serum calcium levels are critical for the correct functioning of multiple vital cellular processes. Accordingly, the regulation of calcium homeostasis is directed at maintaining serum calcium levels within a narrow physiological range. Briefly, hypocalcemia leads to increased parathyroid hormone (PTH) secretion, which stimulates renal calcium reabsorption and bone resorption. PTH also enhances production of the active form of vitamin D, 1,25(OH) 2 vitamin D [1,25(OH) 2 D], which activates the vitamin D receptor (VDR) in the intestine to increase calcium absorption, and in bone to induce bone resorption (1).Because the diet is the only source of calcium to the body, dietary calcium content is critical for calcium homeostasis. At low dietary calcium intake, active calcium transport controlled by 1,25(OH) 2 D predominates, whereas at high calcium intake, calcium is absorbed via passive diffusion. This model is supported by the observation that intestinal calcium transport is reduced in systemic Vdr-null mice, leading to hypocalcemia, hypophosphatemia, and bone abnormalities that include rickets and hyperosteoidosis. The finding that a high calcium/lactose diet prevents this phenotype con-

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Section: Discussionsupporting

confidence: 89%

Section: Introductionmentioning

confidence: 99%

Normocalcemia is maintained in mice under conditions of calcium malabsorption by vitamin D–induced inhibition of bone mineralization

et al. 2012

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“…Harrison and Fraser (22) reported that a low-calcium diet (8 mg/100 g; 0.008%) produces osteoporosis or bone atrophy in rats. They suggested that pure calcium deficiency leads to osteoporosis, while vitamin D deficiency together with calcium deficiency produces osteomalacia in these rats.…”

Section: Discussionmentioning

confidence: 99%

Effects of experimental osteoporosis on alveolar bone loss in rats.

Moriya

Ito

Murai

1998

Journal of Oral Science

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“…Introduction Under the culture condition, nodules with characteristics of normal bone appeared by day 30 regardless Animals fed with a low calcium diet develop osteopoof the calcium conditions. However, the low calcium rosis and bone atrophy [1], and an increase in plasma environment enhanced the mRNA expressions of c-fos, alkaline phosphatase (ALP) activity [2,3]. Earlier we c-jun and osteocalcin, a specific marker of the osteoblast conjectured that a low calcium environment might be phenotype.…”

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confidence: 99%

A Low Calcium Environment Enhances AP-1 Transcription Factor-Mediated Gene Expression in the Development of Osteoblastic MC3T3-E1 Cells

Deyama

Deyama²,

Matsumoto³

et al. 1999

Mineral Electrolyte Metab

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Animals fed a low calcium diet develop hypocalcemia and osteoporotic bone. Earlier we conjectured that a low calcium environment might be one of the factors causing abnormalities in hard tissues. Osteoblastic MC3T3-E1 cells (E1 cells) undergo a process of proliferation and differentiation and then produce small mineralized nodules. In this study, we examined the effects of a low calcium environment on osteoblast-like cells cultured with 10% fetal bovine serum and ascorbic acid. Under the culture condition, nodules with characteristics of normal bone appeared by day 30 regardless of the calcium conditions. However, the low calcium environment enhanced the mRNA expressions of c-fos, c-jun and osteocalcin, a specific marker of the osteoblast phenotype. And the exposure to the low calcium medium inhibited the formation of bone nodules. We further studied the differential expressions of c-fos and c-jun in relation to their responses to serum as a function of phenotypic development in the low calcium environment. Both c-fos and c-jun expressions were highly activated by treatment with epidermal growth factor (EGF), but the magnitude of activation was significantly larger under the low calcium condition than the normal condition at each stage. In addition, DNA-binding activities of activating protein-1 (AP-1), Fos/Jun family dimers, were also accelerated by EGF treatment in the low calcium environment. Our findings suggested that osteocalcin, a bone formation marker, c-fos and c-jun genes, and family protein products (AP-1) interacted to restore the normal cell function which deteriorated in the low calcium environment.

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Bone Structure and Metabolism in Calcium-Deficient Rats

Cited by 106 publications

References 5 publications

Normocalcemia is maintained in mice under conditions of calcium malabsorption by vitamin D–induced inhibition of bone mineralization

Normocalcemia is maintained in mice under conditions of calcium malabsorption by vitamin D–induced inhibition of bone mineralization

Effects of experimental osteoporosis on alveolar bone loss in rats.

A Low Calcium Environment Enhances AP-1 Transcription Factor-Mediated Gene Expression in the Development of Osteoblastic MC3T3-E1 Cells

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