A Possible New Role for Vitamin D-Binding Protein in Osteoclast Control: Inhibition of Extracellular Ca2+Sensing at Low Physiological Concentrations

Adebanjo, Olugbenga A.; Moonga, Baljit S.; Haddad, John G.; Huang, Christopher L.‐H.; Zaidi, Mone

doi:10.1006/bbrc.1998.9037

Cited by 22 publications

(15 citation statements)

References 14 publications

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“…Therefore, the suppression of osteoclast sensitivity to extracellular calcium by DBP may promote bone resorption. However, the precise contribution of this mechanism of DBP action in the pathogenesis of osteoporosis should be viewed with caution, since in these studies in vitro DBP and Gc-MAF were found to be potent inhibitors at concentrations that were almost a million-fold lower than the normal plasma circulating levels [16].…”

Section: Discussionmentioning

confidence: 98%

“…A recent study has suggested that DBP and Gc-MAF are potent inhibitors of extracellular calcium sensing in the osteoclast [16]; extracellular calcium sensing by osteoclasts has been shown to be a powerful antiresorptive signal [17,18]. Therefore, the suppression of osteoclast sensitivity to extracellular calcium by DBP may promote bone resorption.…”

Section: Discussionmentioning

confidence: 99%

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Vitamin D Binding Protein Gene in Male Osteoporosis: Association of Plasma DBP and Bone Mineral Density with (TAAA)n-Alu Polymorphism in DBP

Allcroft

Kanan

et al. 1999

Calcif Tissue Int

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Vitamin D binding protein (DBP) is a major carrier protein for the vitamin D metabolites, but may also play an important role in osteoclast differentiation. Polymorphisms of the DBP gene have been reported, including (TAAA)(n)-Alu repeat polymorphisms downstream of intron 8. We have examined the relationship between polymorphisms of the DBP gene and bone mineral density (BMD) and vertebral fractures in a group of 26 men with vertebral fractures but no underlying secondary cause of osteoporosis (median age 64, ages 27-72 years) and 21 male control subjects (median age 65, ages 40-77 years). There was no apparent effect of DBP phenotype on BMD, but there was a relationship between certain genotypes of (TAAA)(n)-Alu repeats and reduced BMD and vertebral fracture. Lumbar spine and femoral neck BMD were significantly lower in men with 10/8 genotype than 10/10 genotype (P < 0.05). Furthermore, the predominant genotype in men with vertebral fractures was 10/8, whereas the most common genotype in control subjects was 10/10 (odds ratio 56; 95% confidence interval 7-445). Plasma DBP was higher in men with 10/8 genotype than those with 10/10 genotype (P < 0.05), and patients with vertebral fractures were found to have higher levels than control subjects (P < 0.0005). Although our study is small because of the relative rarity of idiopathic osteoporosis in men, the results suggest that (TAAA)(n)-Alu polymorphism may have an important effect on plasma levels of DBP, bone density and fracture risk in men.

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Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

Vitamin D Binding Protein Gene in Male Osteoporosis: Association of Plasma DBP and Bone Mineral Density with (TAAA)n-Alu Polymorphism in DBP

Allcroft

Kanan

et al. 1999

Calcif Tissue Int

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“…DBP also appears to protect the complement factor C5a from proteolytic degradation, effectively enhancing its action as a chemotactic protein [2]. A deglycosylated form of DBP, DBP-macrophage activating factor (DBP-MAF), is able to promote activation of macrophages and osteoclasts, and even native DBP may have effects on osteoclasts [3]. Given both its vitamin D binding characteristics and its potential direct actions on bone resorption, considerable interest has been generated in the scientific community surrounding the potential actions of DBP on bone metabolism and health.…”

Section: Introductionmentioning

confidence: 99%

Vitamin D Binding Protein and Bone Health

Bhan

2014

International Journal of Endocrinology

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Vitamin D binding protein (DBP) is the major carrier protein of 25-hydroxyvitamin D (25(OH) D) in the circulation, where it may serve roles in maintaining stable levels during times of decreased 25(OH) availability and in regulating delivery of 25(OH) D to target tissues. Several genetic polymorphisms of DBP have been described that lead to phenotypic changes in the protein that may affect affinity, activity, and concentration. These polymorphisms have been linked with alterations in bone density in several populations. One of the mechanisms by which DBP may alter bone health involves regulating vitamin D bioavailability. DBP-bound vitamin is thought to be relatively unavailable to target tissues, and thus alterations in DBP levels or affinity could lead to changes in vitamin D bioactivity. As a result, functional vitamin D status may differ greatly between individuals with similar total 25(OH) D levels. Additionally, DBP may have independent roles on macrophage and osteoclast activation. This review will summarize recent findings about DBP with respect to measures of bone density and health.

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“…However, the association of the polymorphisms of these three genes with the BMD and/or osteoporosis has not been established. Vitamin D plays a major role in calcium homeostasis and bone turnover, and vitamin D binding protein (group specific component (GC), alternatively DBP) may play an important role as both a major protein for the vitamin D metabolites and osteoclast differentiation, as well as implicate an association between the polymorphism of vitamin-D binding protein and osteoporosis by bone loss or resorption (Adebanjo et al, 1998). The polymorphisms in Vitamin D binding protein were reported to be associated with lumbar spine BMD, BMI, plasma DBP, IGF-1 and femoral neck BMD (Rapado et al, 1999).…”

Section: Introductionmentioning

confidence: 99%

Association of Interleukin 10 Haplotype with Low Bone Mineral Density in Korean Postmenopausal Women

Park¹,

Han²,

Lee³

et al. 2004

BMB Reports

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Osteoporosis is a disease characterized by exaggerated loss of bone mass, with as much as 50 to 85% of the variation in bone mineral density (BMD) commonly accepted as being genetically determined. Although intensive studies have attempted to elucidate the genetic effects of polymorphisms on BMD and/or osteoporosis in several genes, the genes involved are still largely unknown. The possible associations of genetic variants in five-candidate genes (IL10, CCR3, MCP1, MCP2 and GC) with spinal BMD were investigated in Korean postmenopausal women (n = 370). Fourteen SNPs in five candidate genes were genotyped, and the haplotypes of each gene constructed. The associations of adjusted spinal BMD by age, year since menopause (YSM) and body mass index (BMI), with genetic polymorphisms, were analyzed using multiple regression models. Genetic association analysis of Korean postmenopausal women revealed that IL10 -592A > C and/or IL10 ht2 were associated with decreased bone mass, whereas no significant associations were observed with all polymorphisms in other genes. The levels of spinal BMD in individuals bearing the IL10 -592CC genotype were lower (0.78 ± 0.16) than those in others (0.85 ± 0.17) (P = 0.02), and the BMD of IL10 ht2 bearing individuals were also lower (0.82 ± 0.15) than those in others (0.85 ± 0.17) (P = 0.04). Our results suggest that variants of IL10 might play a role in the decreased BMD, although additional study might need to be followed-up in a more powerful cohort.

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A Possible New Role for Vitamin D-Binding Protein in Osteoclast Control: Inhibition of Extracellular Ca2+Sensing at Low Physiological Concentrations

Cited by 22 publications

References 14 publications

Vitamin D Binding Protein Gene in Male Osteoporosis: Association of Plasma DBP and Bone Mineral Density with (TAAA)n-Alu Polymorphism in DBP

Vitamin D Binding Protein Gene in Male Osteoporosis: Association of Plasma DBP and Bone Mineral Density with (TAAA)n-Alu Polymorphism in DBP

Vitamin D Binding Protein and Bone Health

Association of Interleukin 10 Haplotype with Low Bone Mineral Density in Korean Postmenopausal Women

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