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Review
. 2007:45:539-62.
doi: 10.1007/978-1-4020-6191-2_21.

Calcium signalling and calcium transport in bone disease

H C Blair  1 , P H Schlesinger, C L H Huang, M Zaidi
Affiliations
Review

Calcium signalling and calcium transport in bone disease

H C Blair et al. Subcell Biochem. 2007.

Abstract

Calcium transport and calcium signalling mechanisms in bone cells have, in many cases, been discovered by study of diseases with disordered bone metabolism. Calcium matrix deposition is driven primarily by phosphate production, and disorders in bone deposition include abnormalities in membrane phosphate transport such as in chondrocalcinosis, and defects in phosphate-producing enzymes such as in hypophosphatasia. Matrix removal is driven by acidification, which dissolves the mineral. Disorders in calcium removal from bone matrix by osteoclasts cause osteopetrosis. On the other hand, although bone is central to management of extracellular calcium, bone is not a major calcium sensing organ, although calcium sensing proteins are expressed in both osteoblasts and osteoclasts. Intracellular calcium signals are involved in secondary control including cellular motility and survival, but the relationship of these findings to specific diseases is not clear. Intracellular calcium signals may regulate the balance of cell survival versus proliferation or anabolic functional response as part of signalling cascades that integrate the response to primary signals via cell stretch, estrogen, tyrosine kinase, and tumor necrosis factor receptors.

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Figures

Figure 1
Figure 1
Bulk calcium transport by the osteoblast. While chondrocytes are individual cells embedded in an acellular matrix, and calcify the matrix focally by producing high local concentrations of phosphate, osteoblasts are arrayed in a three-dimensional organized matrix that allows calcium to be deposited in an efficient site-directed mechanism. The osteoblasts are connected into sheets of cells at the surface of bone by gap junctions containing connexin-43. The osteoblasts secrete an organic matrix comprised mainly of type I collagen, which is oriented in layers alternately along the axis of stretch of the bone and orthogonal to this axis. There are also minor proteins, including the calcium binding low molecular weight protein osteocalcin, which facilitate mineral deposition. Mineral deposition is driven by alkaline phosphatase activity which degrades pyrophosphate. Pyrophosphate can be transported either by membrane transporters including ANKH, or may be produced locally by nucleoside pyrophosphatase (PC-1) activity. The high phosphate produced is balanced by calcium transport and by alkalinization of the mineralization site, which are required for continuing mineral deposition, but the specific transporters involved in these activities are unclear (See Colour Plate 28)
Figure 2
Figure 2
Bulk calcium transport by the osteoclast. Net acid transport is driven by the vacuolar-type H+-ATPase with a specialized large membrane subunit. Transport is balanced by chloride transport, probably involving both a chloride channel (CLIC-5) and a chloride bicarbonate antiporter (CLCN7). Supporting transport processes include chloride-bicarbonate exchange. Insertion of transporters is specific for subcellular locations and involves interaction of transporters with specific cytoskeletal components, including actin (See Colour Plate 29)
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