Cellular responses to 24R,25-dihydroxyvitamin D3 in bone and cartilage

B. D. Boyan, J. Hurst-Kennedy, T. A. Denison, Z. Schwartz

Research output: Contribution to journalReview article

Abstract

In this review, we will summarize recent findings surrounding the physiological actions of 24R,25-dihydroxyvitamin D3 [24,25(OH) 2D 3], an active vitamin D3 metabolite that regulates endochondral ossification and bone fracture healing. 24,25(OH) 2D 3 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) 2D 3 reduces production of acid matrix metalloproteinases (MMP), specifically stabilizing neutral MMPs in extracellular matrix vesicles. Recent work has shown that 24,25(OH) 2D 3 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) 2D 3-mediated stimulation of lysophosphatidic acid (LPA) signaling. In bone, immature osteoblasts respond to 24,25(OH) 2D 3, whereas more mature osteoblasts do not. This implicates 24,25(OH) 2D 3 in the maintenance of bone and suggests that its actions are maturation stage-dependent. Collectively, these studies show that 24,25(OH) 2D 3 regulates less mature chondrocytes and osteoblasts through rapid activation of its membrane-associated receptor, establishing it as an important modulator of endochondral ossification.

Original languageEnglish (US)
Pages (from-to)137-142
Number of pages6
JournalImmunology, Endocrine and Metabolic Agents in Medicinal Chemistry
Volume9
Issue number3
DOIs
StatePublished - Dec 1 2009

Keywords

  • 24R,25-dihydroxyvitamin D3
  • Chondrocytes
  • Osteoblasts
  • Vitamin D metabolites

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Immunology and Allergy
  • Pharmacology

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