Abstract
Long non-coding RNAs (lncRNAs) have emerged as promising novel modulators during osteogenesis in mesenchymal stem cells (MSCs). Enhanced SATB2 has been demonstrated to promote osteogenic differentiation of bone marrow-derived mesenchymal stem cells (hBMSCs) in patients with osteonecrosis. Preliminary bioinformatic analysis identified putative binding sites between microRNA-34c (miR-34c) and metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) or miR-34c and SATB2 3’UTR. Thus, the current study aimed to clarify the potential functional relevance of MALAT1-containing exosomes from BMSCs in osteoporosis. The extracted exosomes from primary BMSCs were co-cultured with human osteoblasts (hFOB1.19), followed by evaluation of the hFOB1.19 cell proliferation, alkaline phosphatase (ALP) activity and mineralized nodules. The obtained findings indicated that BMSC-Exos promoted the expression of SATB2 in osteoblasts, and SATB2 silencing reduced the ALP activity of osteoblasts and mineralized nodules. MALAT1 acted as a sponge of miR-34c to promote the expression of SATB2. Additionally, BMSCs-derived exosomal MALAT1 promoted osteoblast activity. Moreover, in vivo experiments indicated that miR-34c reversed the effect of MALAT1, and SATB2 reversed the effect of miR-34c in ovariectomized mice. Taken together, this study demonstrates that BMSCs-derived exosomal MALAT1 enhances osteoblast activity in osteoporotic mice by mediating the miR-34c/SATB2 axis.
Highlights
Osteoporosis remains a significant medical and socioeconomic challenge worldwide, characterized by the systemic impairment of bone mass, and microarchitecture, which enhances the propensity of fragility fractures [1]
In recent years, promising therapeutic approaches to treat osteoporosis are mainly focused on targeting the functions of skeletal stem cells and osteoblasts, which has been proved to be effective in promoting bone formation [2]
We demonstrate that Bone marrow-derived mesenchymal stem cells (BMSCs)-Exos carrying metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) could effectively stimulate the osteoblast activity
Summary
Osteoporosis remains a significant medical and socioeconomic challenge worldwide, characterized by the systemic impairment of bone mass, and microarchitecture, which enhances the propensity of fragility fractures [1]. Osteoblasts arise from several types of skeletal stem cells, including skeletal, mesenchymal stem cells (MSCs), with osteogenic differentiation potential [2]. MSCs can differentiate into osteoblasts, chondrocytes, marrow stromal cells, fat cells, tendon cells, and myocytes [3]. Bone marrow-derived mesenchymal stem cells (BMSCs) are crucial components in process of new bone formation. In the bone marrow stroma, adipocytes share a common precursor, with an imbalance between osteogenesis and adipogenesis of BMSCs capable of resulting in osteoporosis [5]. The discovery of pivotal pathways regulating bone resorption and formation has identified novel approaches with unique mechanisms of action [6]
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