EPC‐derived exosomes promote osteoclastogenesis through LncRNA‐MALAT1

Abstract

Bone repair involves bone resorption through osteoclastogenesis and the stimulation of neovascularization and osteogenesis by endothelial progenitor cells ( EPC s). However, the role of EPC s in osteoclastogenesis is unclear. In this study, we assess the effects of EPC ‐derived exosomes on the migration and osteoclastic differentiation of primary mouse bone marrow‐derived macrophages ( BMM s) in vitro using immunofluorescence, western blotting, RT ‐ PCR and Transwell assays. We also evaluated the effects of EPC ‐derived exosomes on the homing and osteoclastic differentiation of transplanted BMM s in a mouse bone fracture model in vivo. We found that EPC s cultured with BMM s secreted exosomes into the medium and, compared with EPC s, exosomes had a higher expression level of Lnc RNA ‐ MALAT 1. We confirmed that Lnc RNA ‐ MALAT 1 directly binds to miR‐124 to negatively control miR‐124 activity. Moreover, overexpression of miR‐124 could reverse the migration and osteoclastic differentiation of BMM s induced by EPC ‐derived exosomes. A dual‐luciferase reporter assay indicated that the integrin ITGB 1 is the target of miR‐124. Mice treated with EPC ‐derived exosome‐ BMM co‐transplantations exhibited increased neovascularization at the fracture site and enhanced fracture healing compared with those treated with BMM s alone. Overall, our results suggest that EPC ‐derived exosomes can promote bone repair by enhancing recruitment and differentiation of osteoclast precursors through Lnc RNA ‐ MALAT 1.

Exosome-Derived LncRNAs in Lung Cancer

“…These studies suggest that exosomal MALAT1 may act as a non-invasive biomarker for diagnosis of NSCLC or be a promising therapeutic target for NSCLC. At the same time, a similar mechanism of exosomal MALAT1 in many other malignancies is also verified (130)(131)(132). As shown in Table 1, several lncRNAs have been discovered in lung cancer, which are involved in the progression, metastasis, invasion, and proliferation of tumor.…”

Therapeutic potential of extracellular vesicle‐associated long noncoding RNA

“…MALAT1 was found to sequester miR‐124 and subsequently upregulate integrin subunit β1 as well as promote neovascularization at the bone fracture site in an in vivo mouse bone fracture model. Healing was improved in mice treated with these MALAT1‐containing exosomes compared to those administered from bone marrow‐derived macrophages 43 . In addition, Tang et al found that lncRNA OG interacts with heterogeneous nuclear ribonucleoprotein K to regulate the expression of BMP family proteins to promote osteogenic differentiation of bone marrow‐derived MSCs 44 .…”

“…Although there have been relatively few studies as of this writing, this method has been the most popular. Adult stem/stromal cells 32,33,56,57 and progenitor cells 43 are common choices due to their inherent regenerative properties. This approach is advantaged by its straightforward nature; however, potency of unmodified EVs may be limited, resulting in the need for high EV doses that could induce undesired effects.…”

Exosomes as a Novel Approach to Reverse Osteoporosis: A Review of the Literature

“…AREG, a tumor-derived exosome, can activate the epidermal growth factor receptor (EGFR) pathway in pre-osteoclasts to increase RANKL expression. LncRNA-MALAT 1 from endothelial progenitor cells (EPCs) promote osteoclastogenesis through directly binding to miRNA-124 (Cui et al, 2019). Expression of NFATc1, a downstream signal of RANK, is suppressed by miRNA-124 (Lee et al, 2013).…”