Cellular Responses to 24R,25-dihydroxyvitamin D3 in Bone and Cartilage

Author(s): B. D. Boyan, J. Hurst-Kennedy, T. A. Denison, Z. Schwartz

Journal Name: Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Under Re-organization)
(Formerly Current Medicinal Chemistry - Immunology, Endocrine & Metabolic Agents)

Volume 9 , Issue 3 , 2009

Abstract:

In this review, we will summarize recent findings surrounding the physiological actions of 24R,25- dihydroxyvitamin D3 [24,25(OH)2D3], an active vitamin D3 metabolite that regulates endochondral ossification and bone fracture healing. 24,25(OH)2D3 exerts rapid effects in resting zone growth plate chondrocytes through activation of a membrane-associated receptor. One consequence of this activation is rapid inhibition of phospholipase A2, resulting in altered membrane fluidity and arachidonic acid turnover. In addition, phospholipase D activity is increased, leading to increased diacylglycerol and protein kinase C (PKC) activation, as well as PKC-dependent matrix synthesis and chondrocyte maturation. 24,25(OH)2D3 reduces production of acid matrix metalloproteinases (MMP), specifically stabilizing neutral MMPs in extracellular matrix vesicles. Recent work has shown that 24,25(OH)2D3 also has an anti-apoptotic function, acting to protect rat growth plate chondrocytes and mouse ATDC5 cells from apoptosis induced by inorganic phosphate (Pi). Studies using rat costochondral resting zone chondrocytes indicate that the mechanism involves 24,25(OH)2D3-mediated stimulation of lysophosphatidic acid (LPA) signaling. In bone, immature osteoblasts respond to 24,25(OH)2D3, whereas more mature osteoblasts do not. This implicates 24,25(OH)2D3 in the maintenance of bone and suggests that its actions are maturation stage-dependent. Collectively, these studies show that 24,25(OH)2D3 regulates less mature chondrocytes and osteoblasts through rapid activation of its membrane-associated receptor, establishing it as an important modulator of endochondral ossification.

Keywords: Vitamin D metabolites, 24R, 25-dihydroxyvitamin D3, chondrocytes, osteoblasts

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Article Details

VOLUME: 9
ISSUE: 3
Year: 2009
Page: [137 - 142]
Pages: 6
DOI: 10.2174/187152209789760477
Price: $58

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