Zanthoxylum nitidum extract attenuates BMP-2-induced inflammation and hyperpermeability

Abstract

Bone morphogenetic protein-2 (BMP-2) is commonly applied in spinal surgery to augment spinal fusion. Nevertheless, its pro-inflammatory potential could induce dangerous side effects such as vascular hyper-permeability, posing the need for manners against this condition. This study aims to investigate the protective effect of Zanthoxylum nitidum (ZN) on BMP-2 related hyperpermeability and inflammation on the human umbilical vein endothelial cells (HUVECs). The results revealed that, in a concentration-dependent manner, BMP-2 enhanced the production of pro-inflammatory cytokines, including interleukin (IL)-1α, IL-1β, and tumor necrosis factor-α, which were, however, suppressed by ZN. ZN inhibited BMP-2-induced inflammatory response by suppressing the phosphorylation of NF-κBp65 and IκB, and the abnormal nuclear translocation of p65. Moreover, the inhibited expression intercellular tight junction protein VE-cadherin and Occludin caused by BMP-2 was blocked by ZN. The hyper-permeability of HUVECs induced by BMP-2, as expressed as the higher fluorescent intensity of dextran, was also reversed by ZN. Overall, these findings demonstrated that ZN antagonized BMP2-induced inflammation and hyperpermeability. It could be a therapeutic candidate for the treatment of BMP-2-induced side effects during spinal fusion.

Nobiletin, a NF‐κB signaling antagonist, promotes BMP ‐induced bone formation

“…Recent data that BMP‐2 also induces inflammation have also been described 26 . One possible mechanism of inflammation induced by BMP‐2 is the production of inflammatory cytokines such as interleukin (IL)‐1α, IL‐1β, and TNF‐α 27 . We, therefore, speculate that NOB could enhance bone formation by reducing inflammation related to surgery and BMP‐2.…”

“… 26 One possible mechanism of inflammation induced by BMP‐2 is the production of inflammatory cytokines such as interleukin (IL)‐1α, IL‐1β, and TNF‐α. 27 We, therefore, speculate that NOB could enhance bone formation by reducing inflammation related to surgery and BMP‐2. Osteoclasts also reside in BMP‐2‐induced ectopic bones where marrow cavities (Figure 3C ) are present.…”

Polydopamine-Coated Poly(l-lactide) Nanofibers with Controlled Release of VEGF and BMP-2 as a Regenerative Periosteum

“…The inhibitory effect of BMP-2 on VE-cadherin has also been reported in studies related to complications of BMP-2. These studies considered that in BMP-2 induced inflammation, increased vascular permeability is caused by the downregulation of VE-cadherin and occludin, leading to inflammatory exudation. , However, after the combined utilization of VEGF and BMP-2, the effect of inducing angiogenic differentiation was stronger than that of the VP@PLLA group. The reason for this is unclear.…”