Inflammatory cytokines (IL-1α, TNF-α) and LPS modulate the Ca²⁺ signaling pathway in osteoblasts

Abstract

Locally derived growth factors and cytokines in bone play a crucial role in the regulation of bone remodeling, i.e., bone formation and bone resorption processes. We studied the effect of interleukin (IL)-1α, tumor necrosis factor (TNF)-α, and Escherichia coli lipopolysaccharide (LPS) on the hormone-activated Ca2+ message system in the osteoblastic cell line UMR-106 and in osteoblastic cultures derived from neonatal rat calvariae. In both cell preparations, IL-1α, TNF-α, and LPS did not alter basal intracellular Ca2+ concentration ([Ca2+]i) but attenuated Ca2+ transients evoked by parathyroid hormone (PTH) and PGE2 in a dose (1–100 ng/ml)- and time (8–24 h)-dependent fashion. The cytokines modulated hormonally induced Ca2+ influx (estimated by using Mn2+ as a surrogate for Ca2+) as well as Ca2+ mobilization from intracellular stores. The latter was linked to suppressed production of hormonally induced inositol 1,4,5-trisphosphate. The effect of cytokines on [Ca2+]iwas abolished by the tyrosine kinase inhibitor herbimycin A (50 ng/ml). The cytokine’s effect was, however, independent of nitric oxide (NO) production, since NO donors (sodium nitroprusside) as well as permeable cGMP analogs augment, rather than attenuate, hormonally induced Ca2+ transients in osteoblasts. Given the stimulatory role of cytokines on NO production in osteoblasts, the disparate effects of cytokines and NO on the Ca2+ signaling pathway may serve an autocrine/paracrine mechanism for modulating the effect of calciotropic hormones on bone metabolism.

Tumor Necrosis Factor-α, Sphingomyelinase, and Ceramide Inhibit Store-operated Calcium Entry in Thyroid FRTL-5 Cells

“…Another mechanism of action has been shown in osteoblasts. In these cells, several cytokines, including TNF-␣, inhibited a parathyroid hormone-evoked increase in [Ca 2ϩ ] i by abrogating the parathyroid hormone-induced formation of inositol 1,4,5-trisphosphate (49). However, this effect required at least 8 h of incubation with TNF-␣.…”

Effects of Vitamin E on Bone Biomechanical and Histomorphometric Parameters in Ovariectomized Rats

“…A plethora of local cytokines and lipid mediators such as interleukin (IL)-1, IL-6, tumor necrosis factor-alpha (TNF- α ), lymphotoxin, leukotrienes, and prostaglandins of the E series (PGE) are involved in regulating bone metabolism [6–8]. Ovarian hormone deficiency is associated with increased activation of certain immune cells leading to an increase in inflammatory mediators, such as IL-1 [9, 10], IL-6 [9, 11], and in particular PGE 2 [12–17], which is in part responsible for suppressing osteoblastic activity stimulating osteoclastic differentiation, and activity resulting in an increase in bone resorption [18].…”

“…Vitamin E, a fat-soluble antioxidant [26, 28, 29], has been of particular interest due to its ability to suppress the production of certain proinflammatory mediators such as PGE 2 , TNF- α , IL-1, and IL-6 [30–34] that have been linked to increased bone loss [6–8, 35], and protect against oxidative damage caused by ODFRs [29, 36]. The relationship between vitamin E and bone has been studied to some extent.…”

Signaling pathways of ATP‐induced PGE2 release in spinal cord astrocytes are EGFR transactivation‐dependent

“…And PGE2 could produce hyperalgesia and allodynia in conscious mice (Okuda-Ashitaka et al, 2006;Tsukamoto et al, 2010). Moreover, PGE2 could stimulate the intracellular Ca 21 concentration ([Ca 21 ] i ) in osteoblasts, but this [Ca 21 ] i signaling pathway was attenuated by cytokines, such as TNF-a and IL-1 (Tam et al, 1998). Recently, we found ATP could also induce the upregulation of PGE2 in primary cultured spinal astrocytes.…”