Calcium and disease: molecular determinants of calcium crystal deposition diseases.

Abstract

Deposition of basic calcium phosphate (hydroxyapatite, octacalcium phosphate and tricalcium phosphate) (BCP) and crystalline calcium pyrophosphate dihydrate (CPPD) is associated with a variety of aging-related pathologies, including osteoarthritis, cartilage degeneration and pseudogout. These diseases of calcium deposition serve as some of the best-studied examples of how calcium-regulated changes in gene expression can directly lead to pathogenic consequences. Tissue damage can result when crystals stimulate cells to release matrix-degrading molecules or secrete cytokines that stimulate the release of matrix-degrading molecules. Exposure of cultured cells to crystals induces expression of cellular proto-oncogenes such as c-fos, c-myc and c-jun, by a calcium-dependent mechanism, and this response can be blocked by a potential therapeutic compound, phosphocitrate. Activation of the c-fos and c-jun genes is directly involved in expression of metalloproteinases such as collagenase and stromelysin, suggesting that crystal-mediated activation of these genes is directly involved in pathogenesis. In this review recent advances in the molecular mechanisms responsible for crystal-mediated cell activation are discussed.

• Authors: R P Misra
• Journal: Cellular and molecular life sciences : CMLS (Cell Mol Life Sci) Vol. 57 Issue 3 Pg. 421-8 (Mar 2000) ISSN: 1420-682X [Print] Switzerland
• PMID: 10823243 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S., Review)

Chemical References

• Calcium

Topics

• Animals
• Calcinosis (genetics, metabolism)
• Calcium (metabolism)
• Gene Expression Regulation
• Humans
• Signal Transduction