Omentin-1 prevents inflammation-induced osteoporosis by downregulating the pro-inflammatory cytokines

Abstract

Osteoporosis is a frequent complication of chronic inflammatory diseases and increases in the pro-inflammatory cytokines make an important contribution to bone loss by promoting bone resorption and impairing bone formation. Omentin-1 is a newly identified adipocytokine that has anti-inflammatory effects, but little is known about the role of omentin-1 in inflammatory osteoporosis. Here we generated global omentin-1 knockout (omentin-1−/−) mice and demonstrated that depletion of omentin-1 induces inflammatory bone loss-like phenotypes in mice, as defined by abnormally elevated pro-inflammatory cytokines, increased osteoclast formation and bone tissue destruction, as well as impaired osteogenic activities. Using an inflammatory cell model induced by tumor necrosis factor-α (TNF-α), we determined that recombinant omentin-1 reduces the production of pro-inflammatory factors in the TNF-α-activated macrophages, and suppresses their anti-osteoblastic and pro-osteoclastic abilities. In the magnesium silicate-induced inflammatory osteoporosis mouse model, the systemic administration of adenoviral-delivered omentin-1 significantly protects from osteoporotic bone loss and inflammation. Our study suggests that omentin-1 can be used as a promising therapeutic agent for the prevention or treatment of inflammatory bone diseases by downregulating the pro-inflammatory cytokines.

Iron oxides nanoparticles (IOs) exposed to magnetic field promote expression of osteogenic markers in osteoblasts through integrin alpha-3 (INTa-3) activation, inhibits osteoclasts activity and exerts anti-inflammatory action

“…Thus, modulation of macrophages activity has become interesting alternative for the inhibition of bone resorption in osteoporotic patients. That thesis is supported by the recent research performed by Rao et al [10] who discovered that downregulation of pro-inflammatory cytokines prevents inflammation induced osteoporosis. Also, macrophages directly participate in the formation and activation of osteoclasts [11].…”

Increased Release of Proinflammatory Proteins in Primary Human Adipocytes and Activation of the Inflammatory NFĸB, p38, and ERK Pathways upon Omentin Treatment

“…In addition, Song et al administered omentin every 2 weeks for a total of 8 weeks via tail vein injection of an adenoviral vector to obese mice followed by the determination of produced proinflammatory cytokines 2 weeks after the last treatment [32]. In contrast, we measured the levels of proinflammatory biomarkers after the treatment of primary human adipocytes with recombinant omentin for 24 h. Other reasons for the differences might be that Rao et al [31] used an inflammatory cell model by treating macrophages with TNF-α and that in the study of Qi et al [33] mice were treated with LPS 3 days after omentin injection. In contrast, we investigated the effect of omentin without a previous or additional proinflammatory stimulus on the secretory process of primary human adipocytes.…”

“…One study aiming to analyze the relevance of omentin for osteoporosis reported that recombinant omentin (at a supraphysiological concentration of 300 µg/mL) suppressed the secretion of proinflammatory proteins including IL-1α, IL-1β, and IL-6 that was induced by TNF-α in mouse macrophages [31]. The same study evaluated the role of omentin in inflammation using an omentin knockout mouse model and showed that the depletion of omentin led to an increase in serum concentrations of IL-1α, TNF-α, and IL-6 [31]. Two additional studies indicated that omentin diminished the levels of proinflammatory cytokines and chemokines including IL-6 and TNF-α in the serum of obese mice [32] or in the lung tissue of LPStreated mice [33].…”

Inhibitory effect of the TSG-6 on the BMP-4/Smad signaling pathway and odonto/osteogenic differentiation of dental pulp stem cells

“…Moreover, it inhibits the osteogenic differentiation of mesenchymal stem cells at a high concentration (17,18). It has been proved to inhibit osteogenesis in a number of previous studies (17,19). Therefore, it was used to simulate the inflammatory microenvironment in the present study.…”

“…Tumor necrosis factor-alpha (TNF-α) is one of the most important factors involved in the process of inflammation (15,16). Moreover, it inhibits the osteogenic differentiation of mesenchymal stem cells at a high concentration (17,18). It has been proved to inhibit osteogenesis in a number of previous studies (17,19).…”