Erxian herbal pair enhances bone formation in infected bone nonunion models and attenuates lipopolysaccharide-induced osteoblastinhibition by regulating miRNA-34a-5p
ABSTRACTBacterium-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 effe...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Taylor & Francis Group
2022-06-01
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| Series: | Bioengineered |
| Subjects: | |
| Online Access: | https://www.tandfonline.com/doi/10.1080/21655979.2022.2085388 |
| _version_ | 1811175380282769408 |
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| author | Li Zhang Yang Zhang Maomao Miao Shaoqi Hu Xuping Wang Lisha Zhao Xiaowen Huang Gang Cao Dan Shou |
| author_facet | Li Zhang Yang Zhang Maomao Miao Shaoqi Hu Xuping Wang Lisha Zhao Xiaowen Huang Gang Cao Dan Shou |
| author_sort | Li Zhang |
| collection | DOAJ |
| description | ABSTRACTBacterium-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. Target prediction identified SMAD2 as a potential target of miRNA-34a-5p. 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. |
| first_indexed | 2024-04-10T19:36:15Z |
| format | Article |
| id | doaj.art-1266840760624afea40dc67110706adc |
| institution | Directory Open Access Journal |
| issn | 2165-5979 2165-5987 |
| language | English |
| last_indexed | 2024-04-10T19:36:15Z |
| publishDate | 2022-06-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Bioengineered |
| spelling | doaj.art-1266840760624afea40dc67110706adc2023-01-30T05:01:59ZengTaylor & Francis GroupBioengineered2165-59792165-59872022-06-01136143391435610.1080/21655979.2022.2085388Erxian herbal pair enhances bone formation in infected bone nonunion models and attenuates lipopolysaccharide-induced osteoblastinhibition by regulating miRNA-34a-5pLi Zhang0Yang Zhang1Maomao Miao2Shaoqi Hu3Xuping Wang4Lisha Zhao5Xiaowen Huang6Gang Cao7Dan Shou8School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou 310053, ChinaInstitute of Orthopadics and Traumatology, the First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310053,ChinaSchool of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou 310053, ChinaSchool of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou 310053, ChinaDepartment of Medicine, Zhejiang Academy of Traditional Chinese Medicine, Hangzhou 310007, ChinaDepartment of Medicine, Zhejiang Academy of Traditional Chinese Medicine, Hangzhou 310007, ChinaDepartment of Medicine, Zhejiang Academy of Traditional Chinese Medicine, Hangzhou 310007, ChinaSchool of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou 310053, ChinaSchool of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou 310053, ChinaABSTRACTBacterium-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. Target prediction identified SMAD2 as a potential target of miRNA-34a-5p. 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.https://www.tandfonline.com/doi/10.1080/21655979.2022.2085388Erxian herbal pairbone repairLPS-induced bone lossMiRNA-34a-5posteoblasts |
| spellingShingle | Li Zhang Yang Zhang Maomao Miao Shaoqi Hu Xuping Wang Lisha Zhao Xiaowen Huang Gang Cao Dan Shou Erxian herbal pair enhances bone formation in infected bone nonunion models and attenuates lipopolysaccharide-induced osteoblastinhibition by regulating miRNA-34a-5p Bioengineered Erxian herbal pair bone repair LPS-induced bone loss MiRNA-34a-5p osteoblasts |
| title | Erxian herbal pair enhances bone formation in infected bone nonunion models and attenuates lipopolysaccharide-induced osteoblastinhibition by regulating miRNA-34a-5p |
| title_full | Erxian herbal pair enhances bone formation in infected bone nonunion models and attenuates lipopolysaccharide-induced osteoblastinhibition by regulating miRNA-34a-5p |
| title_fullStr | Erxian herbal pair enhances bone formation in infected bone nonunion models and attenuates lipopolysaccharide-induced osteoblastinhibition by regulating miRNA-34a-5p |
| title_full_unstemmed | Erxian herbal pair enhances bone formation in infected bone nonunion models and attenuates lipopolysaccharide-induced osteoblastinhibition by regulating miRNA-34a-5p |
| title_short | Erxian herbal pair enhances bone formation in infected bone nonunion models and attenuates lipopolysaccharide-induced osteoblastinhibition by regulating miRNA-34a-5p |
| title_sort | erxian herbal pair enhances bone formation in infected bone nonunion models and attenuates lipopolysaccharide induced osteoblastinhibition by regulating mirna 34a 5p |
| topic | Erxian herbal pair bone repair LPS-induced bone loss MiRNA-34a-5p osteoblasts |
| url | https://www.tandfonline.com/doi/10.1080/21655979.2022.2085388 |
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