Target Genes

Abstract

Genome-wide analyses indicate vitamin D, through its active metabolite 1,25-dihydroxyvitamin D 3 (1,25 (OH) 2 D 3 ) and the vitamin D receptor (VDR), has a potential to regulate the expression of some 3000 genes [1]. However, current evidence indicates that the strongest phenotype exhibited by vitamin-D-deficient humans or animals relates to impaired skeletal health. The first scientific reports in the early 1900s that rickets was due to vitamin D 3 deficiency placed vitamin D as central to the regulation of calcium and phosphate homeostasis. In this context, it appears that the most critical and most widely studied endocrine role of vitamin D is its contribution to the maintenance of plasma calcium and phosphate at physiological levels through regulation of intestinal absorption of dietary calcium and phosphate.A central question, however, is whether vitamin D acts directly on bone tissue to modulate bone mineral homeostasis and bone strength. This question has been difficult to answer conclusively due in part to the direct actions of vitamin D on plasma calcium and phosphate levels, which indirectly affect bone mineralization and structure. One direct action that has been clearly demonstrated is the ability of plasma 1,25(OH) 2 D 3 , at least at supraphysiological levels, to stimulate bone resorption by the activation of osteoclasts [2].The effects of vitamin D deficiency on bone in vivo can apparently be largely corrected by increasing dietary calcium and phosphate [3,4], suggesting that vitamin D is not an absolute requirement for optimal bone health. Indeed, the fact that the osteomalacic phenotype observed in the vitamin D receptor gene knockout (Vdr KO ) mouse can be rescued by feeding a diet containing high levels of calcium and phosphate has led some to conclude that VDR-mediated activity in bone is essentially redundant [5,6]. Others have suggested that actions of VDR in bone may in fact impair mineralization [7,8]. These conclusions are, however, difficult to reconcile against an accumulating large body of evidence indicating that vitamin D activity in bone is critical for bone cell differentiation and optimal mineral status [9e12]. In this chapter, we examine the evidence for direct effects of vitamin D on the bone as a tissue, and its actions on the constituent cells of bone, in particular bone-matrix-forming osteoblasts, osteocytes, and bone-resorbing osteoclasts.There is now evidence that each of the major bone cells is capable of producing 1,25(OH) 2 D 3 from the 25-hydroxyvitamin D 3 (25(OH)D 3 ) precursor, and that this activity is likely to account for the skeletal effects of circulating 25(OH)D 3 (see Fig. 23.1). On the weight of this evidence, we have proposed that bone is an intracrine organ of vitamin D metabolism [13]. The actions of 1,25(OH) 2 D 3 are mediated ultimately by direct effects on individual vitamin-D-responsive genes. However, the effects of vitamin D on bone tissue as a whole are not yet fully understood but are likely due to a combination of direct effects via VDREs, downstr...

A New Species and Genus of Kraussinidae (Brachiopoda) With a Note on Feeding

“…Fig. 13) are long and are capable of reversing their beat, as in thirteen other genera of brachiopods examined (Atkins, 1956 and unpublished work).…”

Mantle chambers and water circulation in the Tridacnidae (Mollusca).

“…As in all Lamellibranchia, the ctenidia contain muscles both in the axes and in the filaments. Full details are given by Atkins (1943). Contraction of longitudinal muscles in the axes causes the entire gill to shorten while that of vertical muscles in the filaments brings about dorso-ventral contraction of the demibranchs.…”

THE DEVELOPMENT OF THE PLEOPODS IN THE YOUNG CRAB STAGES OF PINNOTHERES (CRUSTACEA)

“…The pleopods of the adult female P . pinnotheres resemble those of the adult P. pisunt in hairiness (see Atkins, 1926, pl. 5, figs.…”

“…and carapace length of 0.55 to 0.69 mm. (Atkins, 1955), while the smallest crab taken from its host was a male with carapace width 1.40 mm. ; this must be far from being the first crab stage.…”

“…pinnotheres has a mrapace width of 0.74 to 0.8 mm., and carapace length of 0.9 to 1.0 mm. (Lebour, 1928, p. 538 ;Atkins, 1955, p. 703), while the smallest crab, a female, taken from its host had a carapace width of 1.5 mm. The increase of 0.7 mm.…”