Affiliation:
1. Departments of Orthopaedics,
2. Periodontics,
3. Biochemistry, and
4. Orthodontics, The University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, MS-7774, San Antonio, TX 78229-3900; and
5. Department of Periodontics, Hebrew University Hadassah Faculty of Dental Medicine, Jerusalem, Israel;
Abstract
This review discusses the regulation of growth plate chondrocytes by vitamin D3. Over the past ten years, our understanding of how two vitamin D metabolites, 1α,25-(OH)2D3 and 24R,25-(OH)2D3, exert their effects on endochondral ossification has undergone considerable advances through the use of cell biology and signal transduction methodologies. These studies have shown that each metabolite affects a primary target cell within the endochondral developmental lineage. 1α,25-(OH)2D3 affects primarily growth zone cells, and 24R,25-(OH)2D3 affects primarily resting zone cells. In addition, 24R,25-(OH)2D3 initiates a differentiation cascade that results in down-regulation of responsiveness to 24R,25-(OH)2D3 and up-regulation of responsiveness to 1α,25-(OH)2D3. 1α,25-(OH)2D3 regulates growth zone chondrocytes both through the nuclear vitamin D receptor, and through a membrane-associated receptor that mediates its effects via a protein kinase C (PKC) signal transduction pathway. PKCα is increased via a phosphatidylinositol-specific phospholipase C (PLC)-dependent mechanism, as well as through the stimulation of phospholipase A2 (PLA2) activity. Arachidonic acid and its downstream metabolite prostaglandin E2 (PGE2) also modulate cell response to 1α,25-(OH)2D3. In contrast, 24R,25-(OH)2D3 exerts its effects on resting zone cells through a separate, membrane-associated receptor that also involves PKC pathways. PKCα is increased via a phospholipase D (PLD)-mediated mechanism, as well as through inhibition of the PLA2 pathway. The target-cell-specific effects of each metabolite are also seen in the regulation of matrix vesicles by vitamin D3. However, the PKC isoform involved is PKCζ, and its activity is inhibited, providing a mechanism for differential autocrine regulation of the cell and events in the matrix by these two vitamin D3 metabolites.
Subject
General Dentistry,Otorhinolaryngology
Cited by
70 articles.
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