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

Keeting, Philip E.; Li, Chun Hong; Whipkey, Diana L.; Thweatt, Ray; Xu, Jiaquan; Murty, Madhavi G.; Blaha, John; Graeber, Geoffrey M.

doi:10.1002/(sici)1097-4644(19980201)68:2<237::aid-jcb10>3.0.co;2-c

Cited by 11 publications

(5 citation statements)

References 38 publications

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“…On its own 1,25(OH) 2 D 3 had no effect, whereas it inhibited the effect of TGF-β in the low OA osteoblasts subgroup only. In normal human osteoblasts, 1,25(OH) 2 D 3 was previously shown to inhibit PGE 2 production both alone and in response to TGF-β [60], a situation similar to our low OA osteoblasts subgroup. In contrast, in the mouse osteoblast-like MC3T3-E1 cells, 1,25(OH) 2 D 3 is without effect, whereas it inhibits PGF-2α-induced PGE 2 production [61].…”

Section: Discussionsupporting

confidence: 84%

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et al. 2006

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Osteoarthritis (OA) is characterized by articular cartilage degradation and hypertrophic bone changes with osteophyte formation and abnormal bone remodeling. Two groups of OA patients were identified via the production of variable and opposite levels of prostaglandin E 2 (PGE 2 ) or leukotriene B 4 (LTB 4 ) by subchondral osteoblasts, PGE 2 levels discriminating between low and high subgroups. We studied whether the expression of 5-lipoxygenase (5-LO) or 5-LO-activating protein (FLAP) is responsible for the shunt from prostaglandins to leukotrienes. FLAP mRNA levels varied in low and high OA groups compared with normal, whereas mRNA levels of 5-LO were similar in all osteoblasts. Selective inhibition of cyclooxygenase-2 (COX-2) with NS-398-stimulated FLAP expression in the high OA osteoblasts subgroup, whereas it was without effect in the low OA osteoblasts subgroup. The addition of PGE 2 to the low OA osteoblasts subgroup decreased FLAP expression but failed to affect it in the high OA osteoblasts subgroup. LTB 4 levels in OA osteoblasts were stimulated about twofold by 1,25-dihydroxyvitamin D 3 (1,25(OH) 2 D 3 ) plus transforming growth factor-β (TGF-β), a situation corresponding to their effect on FLAP mRNA levels. Treatments with 1,25(OH) 2 D 3 and TGF-β also modulated PGE 2 production. TGF-β stimulated PGE 2 production in both OA osteoblast groups, whereas 1,25(OH) 2 D 3 alone had a limited effect but decreased the effect of TGF-β in the low OA osteoblasts subgroup. This modulation of PGE 2 production was mirrored by the synthesis of COX-2. IL-18 levels were only slightly increased in a subgroup of OA osteoblasts compared with normal; however, no relationship was observed overall between IL-18 and PGE 2 levels in normal and OA osteoblasts. These results suggest that the shunt from the production of PGE 2 to LTB 4 is through regulation of the expression of FLAP, not 5-LO, in OA osteoblasts. The expression of FLAP in OA osteoblasts is also modulated differently by 1,25(OH) 2 D 3 and TGF-β depending on their endogenous low and high PGE 2 levels.

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Section: Discussionsupporting

confidence: 84%

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et al. 2006

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“…There is now a considerable body of evidence indicating that PLA 2 plays an important role in 1α,25(OH) 2 D 3 –activated membrane-mediated signaling (13,15–18). Melittin and mastasparan are stimulators of PLA 2 that have exhibited similar effects to those of 1α,25(OH) 2 D 3 on PLCβ and PKCα activation (19).…”

Section: Role Of Plaamentioning

confidence: 99%

Membrane-mediated actions of 1,25-dihydroxy vitamin D3: A review of the roles of phospholipase A2 activating protein and Ca2+/calmodulin-dependent protein kinase II

Doroudi

Schwartz

Boyan

2015

The Journal of Steroid Biochemistry and Molecular Biology

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The secosteroid 1α,25-dihydroxy vitamin D3 [1α,25(OH)2D3] acts on cells via classical steroid hormone receptor-mediated gene transcription and by initiating rapid membrane-mediated signaling pathways. In its membrane-initiated pathway, after 1α,25(OH)2D3 interacts with protein disulfide isomerase, family A, member 3 (Pdia3) in caveolae, phospholipase A2 (PLA2) and protein kinase C (PKC) are activated. Recent efforts to determine the signaling proteins involved in the 1α,25(OH)2D3 signal from Pdia3 to PLA2 have indicated that phospholipase A2 activating protein (PLAA) and Ca2+/calmodulin-dependent kinase II (CaMKII) are required. PLAA is located in caveolae, where it interacts with Pdia3 and caveolin-1 (Cav-1) to initiate rapid signaling via CaMKII, activating PLA2, leading to activation of protein kinase C (PKC) and PKC-dependent responses.

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“…Multiple studies have demonstrated the pivotal role PLA 2 plays in 1␣,25(OH) 2 D 3 -dependent membrane-mediated signaling [8,[13][14][15][16]. Stimulation of PLA 2 activity using agents such as bee venom melittin and snake venom mastoparan, mimics the effects of 1␣,25(OH) 2 D 3 on PKC in growth zone chondrocytes.…”

Section: Introductionmentioning

confidence: 99%