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DIFFERENTIAL REGULATION OF GROWTH PLATE CHONDROCYTES BY 1,25-(OH)₂D₃ AND 24R,25-(OH)₂D₃ INVOLVES CELL-MATURATION-SPECIFIC MEMBRANE-RECEPTOR-ACTIVATED PHOSPHOLIPID METABOLISM

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;

Correspondence: ^* corresponding author, BoyanB{at}uthscsa.edu

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, 1,25-(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. 1,25-(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 1,25-(OH)₂D₃. 1,25-(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. PKC 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 1,25-(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. PKC 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 PKC, 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.

Key Words: 1 • 25-(OH)₂D₃ • 24R • 25-(OH)₂D₃ • endochondral ossification • growth plate • chondrocytes • phospholipase A₂ • phospholipase C • phospholipase D

Critical Reviews in Oral Biology & Medicine, Vol. 13, No. 2, 143-154 (2002)
DOI: 10.1177/154411130201300205


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