10.6084/M9.FIGSHARE.21952693.V1
Li Zhang
Li
Zhang
Yang Zhang
Yang
Zhang
Maomao Miao
Maomao
Miao
Shaoqi Hu
Shaoqi
Hu
Xuping Wang
Xuping
Wang
Lisha Zhao
Lisha
Zhao
Xiaowen Huang
Xiaowen
Huang
Gang Cao
Gang
Cao
Dan Shou
Dan
Shou
Erxian herbal pair enhances bone formation in infected bone nonunion models and attenuates lipopolysaccharide-induced osteoblastinhibition by regulating miRNA-34a-5p
<p>Bacterium-induced inflammatory responses cause bone nonunion. Although antibiotics suppress infection, bone loss after antibacterial treatment remains a critical challenge. Erxian herbal pair (EHP) has been proven effective in promoting bone formation. Our study aimed to investigate the effect of EHP on bone repair after anti-infection treatment, explore its effect on a lipopolysaccharide (LPS)-induced osteoblast. We evaluated effects of EHP on bone repair with Micro-CT, and morphology detecting. Chemical constituents of EHP and EHP-containing serum (EHP-CS) were identified by UHPLC-Q/TOF-MS. In addition, osteoblast induced by LPS was established and administrated with EHP-CS. Cell proliferationwas assessed by MTT. <i>Target prediction identified SMAD2 as a</i> <i>potential target of miRNA-34a-5p.</i> MiRNA mimic, inhibitor and siRNA were transiently transfected into osteoblasts. The mRNA levels and protein expressions of miRNA-34a-5p, BMP2, Runx2, SMAD2 were assessed. The results showed that the main biocactivity ingredients in EHP-CS were Baohuoside Ι and Orcinol Glucoside. EHP could promote bone remolding after anti-infection therapy and restore the activity of LPS-induced osteoblasts. Moreover, miRNA-34a-5p was dramatically downregulated and SMAD2 was upregulated after LPS stimulation, while EHP resisted the inhibition of LPS by promoting miRNA-34a-5p, ALP, and BMP2 expressions. Whereas downregulation of miRNA-34a-5p reversed these effects. Silencing endogenous SMAD2 expression markedly promoted BMP2 and ALP activity and enhanced osteogenesis. Taken together, EHP restored LPS-induced bone loss by regulating miRNA-34a-5p levels and repressing its target gene SMAD2. EHP might be a potential adjuvant herbal remedy for the treatment of bone nonunion, and miRNA-34a-5p is a novel target for controlling bone and metabolic diseases.</p>
Biochemistry
Genetics
Molecular Biology
Pharmacology
Ecology
Immunology
Biological Sciences not elsewhere classified
Cancer
Hematology
Taylor & Francis
2023
2023-01-25
2024-03-22
Dataset
85519311 Bytes
10.6084/m9.figshare.21952693
10.1080/21655979.2022.2085388
CC BY 4.0