NDLI: miR-1323 suppresses bone mesenchymal stromal cell osteogenesis and fracture healing via inhibiting BMP4/SMAD4 signaling

Content Provider	Springer Nature : BioMed Central
Author	Xie, Hui Liu, Ming Jin, Yaofeng Lin, Haiqing Zhang, Yushan Zheng, Song
Abstract	Background Atrophic non-union fractures show no radiological evidence of callus formation within 3 months of fracture. microRNA dysregulation may underlie the dysfunctional osteogenesis in atrophic non-union fractures. Here, we aimed to analyze miR-1323 expression in human atrophic non-union fractures and examine miR-1323’s underlying mechanism of action in human mesenchymal stromal cells. Methods Human atrophic non-union and standard healing fracture specimens were examined using H&E and Alcian Blue staining, immunohistochemistry, qRT-PCR, immunoblotting, and ALP activity assays. The effects of miR-1323 mimics or inhibition on BMP4, SMAD4, osteogenesis-related proteins, ALP activity, and bone mineralization were analyzed in human mesenchymal stromal cells. Luciferase reporter assays were utilized to assay miR-1323’s binding to the 3'UTRs of BMP4 and SMAD4. The effects of miR-1323, BMP4, and SMAD4 were analyzed by siRNA and overexpression vectors. A rat femur fracture model was established to analyze the in vivo effects of antagomiR-1323 treatment. Results miR-1323 was upregulated in human atrophic non-union fractures. Atrophic non-union was associated with downregulation of BMP4 and SMAD4 as well as the osteogenic markers ALP, collagen I, and RUNX2. In vitro, miR-1323 suppressed BMP4 and SMAD4 expression by binding to the 3'UTRs of BMP4 and SMAD4. Moreover, miR-1323’s inhibition of BMP4 and SMAD4 inhibited mesenchymal stromal cell osteogenic differentiation via modulating the nuclear translocation of the transcriptional co-activator TAZ. In vivo, antagomiR-1323 therapy facilitated the healing of fractures in a rat model of femoral fracture. Conclusions This evidence supports the miR-1323/BMP4 and miR-1323/SMAD4 axes as novel therapeutic targets for atrophic non-union fractures.
Related Links	https://josr-online.biomedcentral.com/counter/pdf/10.1186/s13018-020-01685-8.pdf
Ending Page	13
Page Count	13
Starting Page	1
File Format	HTM / HTML
DOI	10.1186/s13018-020-01685-8
Journal	Journal of Orthopaedic Surgery and Research
Issue Number	1
Volume Number	15
Language	English
Publisher	BioMed Central
Publisher Date	2020-06-29
Access Restriction	Open
Subject Keyword	Orthopedics Surgical Orthopedics Fracture Atrophic non-union BMP4 SMAD4 miR-1323
Content Type	Text
Resource Type	Article
Subject	Surgery Orthopedics and Sports Medicine
Journal Impact Factor	2.8/2023
5-Year Journal Impact Factor	3/2023

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1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
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4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
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