MicroRNA-21 facilitates osteoblast activity
| Autor: | Makoto Makishima, Liangjun Zhong, Ujjal K. Bhawal, Shunichi Oka, Ri Ma, Nitesh Tewari, Xiaoyan Li, Yi Liu, Fengzhu Zhang |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
musculoskeletal diseases MicroRNA-21 Biophysics Biochemistry Bone remodeling Masson's trichrome stain lcsh:Biochemistry 03 medical and health sciences 0302 clinical medicine microRNA medicine lcsh:QD415-436 Osteopontin lcsh:QH301-705.5 biology Osteoblast differentiation Mouse gene expression microarray Chemistry Osteoblast Staining Cell biology RUNX2 030104 developmental biology medicine.anatomical_structure lcsh:Biology (General) 030220 oncology & carcinogenesis biology.protein Immunohistochemistry Research Article |
| Zdroj: | Biochemistry and Biophysics Reports, Vol 25, Iss, Pp 100894-(2021) Biochemistry and Biophysics Reports |
| ISSN: | 2405-5808 |
| Popis: | MicroRNAs are emerging as critical post-transcriptional modulators in bone remodeling, regulating the functions of osteoblasts and osteoclasts. Intercellular crosstalk between osteoblasts and osteoclasts is mediated by miR-21 that controls the bone homeostasis response, providing potential targets for the maintenance of osteoblast function. The aim of this study was to investigate the effects of miR-21 on osteoblast function, and to explore the underlying mechanism. Increased alkaline phosphatase (ALP) activity and accelerated matrix mineralization was observed in mouse pre-osteoblast MC3T3-E1 cells compared with the non-induction (control) group. MiR-21 positively regulates osteogenic differentiation and mineralization by facilitating the expression of key osteogenic factors (ALP, Runx2, Osteopontin (OPN), Osterix (OSX) and Mef2c) in MC3T3-E1 cells. Furthermore, a deficiency of miR-21 suppresses the expression of those factors at both the mRNA and protein levels, indicating that miR-21 is a positive regulator of osteoblastic differentiation. H-E staining, Azan staining, Masson's Trichrome staining and Toluidine blue staining were performed in jaw and femur tissues of miR-21 knockout (miR-21KO) and wild-type (WT) mice. Immunohistochemical staining revealed substantially lower levels of ALP, Runx2 and OSX expression in jaw and femur tissues of miR-21KO mice. A similar trend was observed in femur tissues using quantitative real-time (RT) PCR. A total of 17 osteogenesis-related mRNAs were found to be differentially expressed in miR-21KO femur tissues using Mouse Gene Expression Microarray analysis. GeneSpring and Ingenuity Pathway Analysis revealed several potential target genes that are involved in bone remodeling, such as IL-1β and HIF-1α. Several important pathways were determined to be facilitators of miR-21, which provides a reliable reference for future studies to elucidate the biological mechanisms of osteoblast function. Taken together, these results lead us to hypothesize a potential role for miR-21 in regulating osteoblast function, thus representing a potential biomarker of osteogenesis. Highlights • miR-21 facilitates osteoblast differentiation. • miR-21 deficiency impairs the osteogenic activity of alveolar bone and femur. • DNA microarrays identify differentially expressed genes with miR-21 deficiency. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|