Abstract
Osteoporosis is a prevalent metabolic bone disease characterized by low bone mineral density and degenerative disorders of bone tissues. Previous studies showed the abnormal osteogenic differentiation of endogenous bone marrow mesenchymal stem cells (BMSCs) contributes to the development of osteoporosis. However, the underlying mechanisms by which BMSCs undergo osteogenic differentiation remain largely unexplored. Recently, long non-coding RNAs have been discovered to play important roles in regulating BMSC osteogenesis. In this study, we first showed MIR22HG, which has been demonstrated to be involved in the progression of several cancer types, played an important role in regulating BMSC osteogenesis. We found the expression of MIR22HG was significantly decreased in mouse BMSCs from the osteoporotic mice and it was upregulated during the osteogenic differentiation of human BMSCs. Overexpression of MIR22HG in human BMSCs enhanced osteogenic differentiation, whereas MIR22HG knockdown inhibited osteogenic differentiation both in vitro and in vivo. Mechanistically, MIR22HG promoted osteogenic differentiation by downregulating phosphatase and tensin homolog (PTEN) and therefore activating AKT signaling. Moreover, we found MIR22HG overexpression promoted osteoclastogenesis of RAW264.7 cells, which indicated that MIR22HG played a significant role in bone metabolism and could be a therapeutic target for osteoporosis and other bone-related diseases.
Highlights
Osteoporosis is one of the most common metabolic bone diseases which results from the disrupted balance between bone formation and resorption[1]
Based on our previous work, expression levels of several interesting genes were chosen to be measured by quantitative reverse transcriptionpolymerase chain reaction (qRT-PCR) and we found many genes were differentially expressed after ovariectomy
The MIR22HG expression level was significantly decreased in OVX mice, the expression level of RUNX2, an osteogenic marker, was significantly decreased in mouse BMSCs (mBMSCs) from OVX mice (Fig. 1e). These results suggested the potential involvement of MIR22HG in the compromised osteogenesis of osteoporotic bone marrow mesenchymal stem cells (BMSCs)
Summary
Osteoporosis is one of the most common metabolic bone diseases which results from the disrupted balance between bone formation and resorption[1]. With the progressive aging of the global population, the incidence of osteoporosis is increasing dramatically which leads to an increased risk of fractures and exerts a strong impact on morbidity, and even mortality[2,3]. The pathological mechanisms of osteoporosis have not been fully understood yet. Growing amounts of evidences have shown that lncRNAs are important regulators in diverse biological processes and diseases including osteoporosis[5,6,7]. A good number of lncRNAs have been demonstrated to play critical roles in the osteogenic differentiation of BMSCs8–10. LncRNA MALAT1 was Official journal of the Cell Death Differentiation Association
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
