1,25-dihydroxyvitamin D3 pretreatment limits prostaglandin biosynthesis by cytokine-stimulated adult human osteoblast-like cells

✍ Scribed by Philip E. Keeting; Chun Hong Li; Diana L. Whipkey; Ray Thweatt; Jiaquan Xu; Madhavi Murty; J. David Blaha; Geoffrey M. Graeber

• Publisher: John Wiley and Sons
• Year: 1998
• Tongue: English
• Weight: 161 KB
• Volume: 68
• Category: Article
• ISSN: 0730-2312
• DOI: 10.1002/(sici)1097-4644(19980201)68:2<237::aid-jcb10>3.0.co;2-c

✦ Synopsis

The steroid derivative 1,25-dihydroxyvitamin D 3 (1,25(OH) 2 D 3 ) is a regulator of bone biology, and there is evidence that 1,25(OH) 2 D 3 modulates arachidonic acid metabolism in osteoblastic cell model systems and in bone organ cultures. In the present studies, 1,25(OH) 2 D 3 decreased prostaglandin (PG) biosynthesis by normal adult human osteoblast-like (hOB) cell cultures by about 30%. The decrease was observed under basal incubation conditions, or in specimens stimulated by transforming growth factor-␤ 1 (TGF-␤) or by tumor necrosis factor-␣ (TNF). The inhibition of the TGF-␤-stimulated PG production appeared to reflect a diminished efficiency of arachidonic acid conversion into PGs by the cells, while the efficiency of substrate utilization for PG biosynthesis was unaffected by 1,25(OH) 2 D 3 pretreatment in the unstimulated samples, or in samples stimulated with TNF or with TNF plus TGF-␤. Free arachidonic acid levels were decreased following 1,25(OH) 2 D 3 pretreatment in the TNF stimulated samples. hOB cell phospholipase A 2 activity was measured in subcellular fractions, and this activity was decreased by 20-25% in the 1,25(OH) 2 D 3 pretreated samples. The addition of the selective inhibitor AACOCF 3 to the phospholipase A 2 assays provided evidence that it was the cytoplasmic isoform of the enzyme that was affected by the 1,25(OH) 2 D 3 pretreatment of the hOB cells. Thus, 1,25(OH) 2 D 3 regulation of hOB cell biology includes significant effects on arachidonic acid metabolism. In turn, this could influence the effects of other hormones and cytokines whose actions include the stimulated production of bioactive arachidonic acid metabolites.