Local suppression of pro-inflammatory cytokines and the effects in BMP-2-induced bone regeneration

Abstract

The objective of this study is to investigate the effect of local inflammation suppression on the bone regeneration. Gelatin hydrogels incorporating mixed immunosuppressive triptolide-micelles and bone morphogenic protein-2 (BMP-2) were prepared. The controlled release of both the triptolide and BMP-2 from the hydrogels was observed under in vitro and in vivo conditions. When either J774.1 macrophage-like or MC3T3-E1 osteoblastic cells were cultured in the hydrogels incorporating mixed 2.5, 5 or 10 mg of triptolide-micelles and BMP-2, the expression level of pro- and anti-inflammatory cytokines including interleukin (IL)-6 and IL-10 was down-regulated, but the alkaline phosphatase (ALP) activity was promoted compared with those of hydrogels incorporating BMP-2 without triptolide-micelles. When implanted into a critical-sized bone defect of rats, the hydrogels incorporating mixed 2.5 or 5 mg of triptolide-micelles and BMP-2 showed significantly lower number of neutrophils, lymphocytes, macrophages or dendritic and mast cells infiltrated into the defect, and lower expression level of IL-6, TNF-α, and IL-10 than those incorporating BMP-2 without triptolide-micelles. The reduced local inflammation responses at the defects implanted with the hydrogels incorporating mixed 2.5 or 5 mg of triptolide-micelles and BMP-2 subsequently enhanced the bone regeneration thereat. It is concluded that the proper local modulation of inflammation responses is a promising way to achieve the enhanced bone regeneration.

Cyclic AMP Response Element-binding Protein H (CREBH) Mediates the Inhibitory Actions of Tumor Necrosis Factor α in Osteoblast Differentiation by Stimulating Smad1 Degradation

“…However, other cytokines, such as IL-6, IL-1␤, and nitric oxide, are also secreted into inflammatory environments and may play different roles in osteogenesis (36 -39). Moreover, local inhibitors of inflammation such as triptolide and BMP-binding peptide, can enhance the osteoinductive efficacy of BMP-2 in vivo (40,41). However, direct evidence supporting an inhibitory effect of inflammation on BMP2-induced osteoblast differentiation is currently lacking.…”

Dual-controlled release system of drugs for bone regeneration

“…For example, Choi et al [169] report on a core-shell structure within microcapsules wherein BMP-2 and dexamethasone (Dex) dominated in either the core or the shell to enable sequential release. Even though the impact of the different release pattern of BMP-2 and Dex was not tested in this work, the gene expression levels of osteogenic markers were found to be Ratanavaraporn et al [174] design dual release of BMP-2 and triptolide of an antiinflammatory drug and evaluate their effect on bone regeneration. When implanted into a criticalsized bone defect, the hydrogel incorporating mixed BMP-2 and triptolide showed a significantly lower the expression level of pro-inflammatory cytokines than that incorporating BMP-2 alone, resulting in enhanced bone regeneration.…”

Accelerated Healing of Full-Thickness Wounds by Genipin-Crosslinked Silk Sericin/PVA Scaffolds

“…However, the number of macrophages and giant cells is related to scar formation [Druecke et al, 2004]. High numbers of macrophages and giant cells are responsible for localized inflammatory reactions that could suppress further stages of wound healing and subsequently lead to scar formation [Druecke et al, 2004;Ratanavaraporn et al, 2012]. Thus, the higher number of macrophages and giant cells in wounds treated with the genipin-crosslinked PVA scaffolds without sericin could delay wound healing compared with the genipin-crosslinked sericin/ PVA scaffolds.…”