Naringin promotes differentiation of bone marrow stem cells into osteoblasts by upregulating the expression levels of microRNA-20a and downregulating the expression levels of PPARγ

Abstract

Naringin is a dihydrotestosterone flavonoid compound that significantly inhibits bone loss, improves bone density, and enhances biomechanical anti‑compression performance. Previous studies have demonstrated that naringin improves the activity levels of osteocalcin (OC) and alkaline phosphatase (ALP) in MC3T3‑E1 osteoblast precursor cells. The present study investigated the effects of naringin on osteoblastic differentiation and inhibition of adipocyte formation in bone marrow stem cells (BMSCs). The levels of osteogenesis were modulated via upregulation of the expression levels of microRNA (miR)‑20a, and downregulation of the expression levels of peroxisome proliferator‑activated receptor γ (PPARγ). The results indicated that naringin significantly enhanced BMSC proliferation in a dose‑dependent manner. In addition, naringin significantly increased the mRNA expression levels of OC, ALP, and collagen type I. Furthermore, naringin decreased the protein expression levels of PPARγ, and increased the expression levels of miR‑20a in the BMSCs. These results suggested that miR‑20a may regulate the expression of PPARγ in BMSCs. To our knowledge, this is the first study to report naringin‑induced osteogenesis via upregulation of the expression levels of miR‑20a, and downregulation of the expression levels of PPARγ. These results indicated the important role of naringin in BMSC differentiation.

Effects of yuja peel extract and its flavanones on osteopenia in ovariectomized rats and osteoblast differentiation

“…Citrus flavanones affect bone resorption and bone formation [, ]. However, the effect of yuja on bone health has not been explored, despite its many established health benefits.…”

“…These compounds have anti-inflammatory, anti-diabetic, anti-platelet, and antioxidant activities [5,[7][8][9]. Citrus flavanone glycosides, such as hesperidin and naringin, are the most abundant compounds in yuja peel, and inhibit osteopenia in ovariectomy (OVX)-induced rat bone loss models by reducing the number of osteoclasts and improving osteoblastogenesis [10][11][12][13][14][15]. Yuja peel contains higher flavanone contents (48 mg/100 g) compared to lemon (26 mg/100 g) [7,16].…”

Vitamin K2 promotes mesenchymal stem cell differentiation by inhibiting miR-133a expression

“…Accumulating evidence suggests that miRNAs are involved in osteoblast differentiation. Previous studies have revealed that miRNA (miR)-20a is upregulated in naringin-induced osteogenesis in bone marrow stromal cells (BMSCs) (5) and that inhibition of miR-103a increased runt-related transcription factor 2 (Runx2) protein expression levels in osteoblasts (6). A recent study has demonstrated that miR-21 promotes osteogenesis and mineralization in MC3T3-E1 cells by inhibiting the translation of mothers against decapentaplegic 7 (7).…”

Effect of MicroRNA-20a on Osteogenic Differentiation of Human Adipose Tissue-Derived Stem Cells

“…Similarly, Western blot analysis revealed that miR-20a promoted the expression of ALP protein. Previous studies [Zhang et al, 2011;Fan et al, 2015;Zhou et al, 2015] confirmed that miR-20a promoted cell osteogenic differentiation by inhibiting the target gene PPARγ and upregulating the osteogenic signaling pathway components BMP/RUNX2. The Western blot results showed that the PPARγ protein was decreased, and RUNX2 protein was increased in the miR-20a overexpression group.…”

“…Zhang et al [2011] indicated that miR-20a promoted human bone marrow-derived mesenchymal stem cell (BMSC) osteogenic differentiation and activated the BMP/RUNX2 signaling pathway via downregulating the expression of peroxisome proliferator-activated receptor γ (PPARγ) and inhibiting the expression of Bambi and Crim1, antagonists of the BMP pathway. Another study [Fan et al, 2015] showed that naringin enhanced the BMSC transi-tion into osteoblasts, and the mechanism involved miR-20a suppression of PPARγ expression in BMSCs. miR-20a can promote the osteogenic process of inflammatory periodontal ligament cells as well [Yang et al, 2016].…”