miR‑27a‑3p negatively regulates osteogenic differentiation of MC3T3‑E1 preosteoblasts by targeting osterix

Abstract

osteoporosis is a complex multifactorial disorder characterized by microarchitectural deterioration, low bone mass, and increased risk of fractures or broken bones. Balanced bone remodeling is tightly regulated by the differentiation, activity and apoptosis of bone-forming osteoblasts and bone-resorbing osteoclasts. Micrornas (mirs) are dysregulated in osteoporosis, but whether they control osteogenic differentiation and skeletal biology, or could serve as therapeutic targets remains to be elucidated. The present study identified miR-27a-3p as a critical suppressor of osteoblastogenesis. Bioinformatics analysis and luciferase reporter assays demonstrated that miR-27a-3p directly targeted and controlled the expression of osterix (osx), an early response gene essential for bone formation, through its 3'-untranslated region. miR-27a-3p functionally inhibited the differentiation of preosteoblasts by decreasing osx expression, which synergistically contributed to bone formation. miR-27a-3p level was significantly decreased during osteogenic differentiation and increased in the serum of patients with osteoporosis. Together, miR-27a-3p contributed to diminished osteogenic function during osteogenic differentiation and might thus serve as a therapeutic target and diagnostic biomarker for osteoporosis.

MicroRNAs Possibly Involved in the Development of Bone Metastasis in Clear-Cell Renal Cell Carcinoma

“…Serum levels of miR-27a-3p are elevated in pancreatic cancer, CRC, and PC, demonstrating its potential as a non-invasive biomarker [ 143 , 144 , 145 ]. miR-27a-3p is involved in bone metabolism and negatively regulates osteogenic differentiation [ 146 ]. It is part of the aforementioned 23a/27a/24-2 miRNA cluster, which is involved in both oncogenesis and osteoblast differentiation by targeting RUNX2 and SATB2 [ 34 ].…”

Roles of MicroRNAs in Osteogenesis or Adipogenesis Differentiation of Bone Marrow Stromal Progenitor Cells

“…Similarly, microRNA-27a-3p was upregulated in the serum of patients with osteoporosis. Further experiments have proven that microRNA-27a-3p functionally represses the osteoblast differentiation by directly binding to OSX, which synergistically promotes osteogenesis and bone formation [107].…”

Application of microRNA in Human Osteoporosis and Fragility Fracture: A Systemic Review of Literatures

“…Comparison between osteoporotic patients and controls [ 16 , 20 , 22 , 24 , 27 , 29 , 31 , 32 , 34 , 35 , 36 , 40 , 41 , 44 , 45 , 47 , 50 , 51 , 52 , 53 , 55 , 59 , 61 , 63 ]…”

“…MiR-27a-3p, miR-96, and miR-637 target osterix, inhibiting osteogenic differentiation [ 26 , 59 ]. The experiment of a mice model showed that repetitively agomiR-96-injected young mice had significantly decreased BMD compared with vehicle-treated mice, and aged mice treated with antagomir-96 had higher bone strength compared to controls [ 26 ].…”

“… * It is noteworthy that miR-27a-3p is found to target both osterix and ATF3 gene with opposite effect on osteoblastogenesis. In Fu et al 2019, human MSCs transfected with miR-27a-3p mimics have higher activity of osteogenic differentiation [ 35 ]; whereas MC3T3-E1 cells transfected with miR-27a-3p mimics have decreased expression of osteoblast marker genes in Xu et al 2020 [ 59 ]. MRC2, mannose receptor C type 2; Mef2c, myocyte enhancer factor 2c; ATF3, activating transcription factor 3; PCSK5, proprotein convertase subtilisin/kexin type 5 …”