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Long Non-coding RNA SNHG1 Suppresses the Osteogenic Differentiation of Bone Marrow Mesenchymal Stem Cells by Binding
Kaihua Pan1, Yuanyuan Lu1, Daning Cao1
1Department of Orthopaedics, The First Hospital of Changsha, No. 311, Yingpan Road, Kaifu District, Changsha, 410005, Hunan, People's Republic of China.
Abstract:
Osteoporosis (OP) has a significant detrimental impact on the health of the elder. Long-term clinical effectiveness of current drugs used for OP treatment is limited. Therefore, it is very important to explore novel treatment targets for OP. The expression of SNHG1, HMGB1, OCN and OPN in gene level was measured using RT-qPCR, and the protein expression was determined by Western blotting assay. The concentration of IL-1β and IL-18 in supernatant of the bone marrow mesenchymal stem cells (BMSCs) was measured by ELISA. The interaction between SNHG1 and HMGB1 was confirmed by RNA pull down. Besides, alizarin red staining was performed to evaluate the differentiation of BMSCs into osteoblast. SNHG1 and HMGB1 were found to be upregulated in the serum of OP patients. During the osteogenic differentiation of BMSCs, the expression of osteoblastogenesis markers (OCN and OPN) and the activity of ALP were upregulated, while the expression levels of SNHG1 and HMGB1 were decreased in a time-dependent manner. In addition, the interaction between SNHG1 and HMGB1, expression of pyroptosis-associated factors (caspase-1 p20 and GSDMD-N), and secretion of IL-1β and IL-18 were also decreased during osteogenic differentiation. Interestingly, increasing SNHG1 promoted HMGB1 expression, activated pyroptosis, but inhibited osteogenic differentiation. Silencing HMGB1 or inhibiting caspase-1 partially rescued the inhibitory effect of SNHG1 on osteogenic differentiation. Our findings indicate that SNHG1 suppresses the osteogenic differentiation of BMSCs by activating pyroptosis through interaction with HMGB1 and promotion of HMGB1 expression. Our work provides further evidence supporting SNHG1 acts as a potential target for OP treatment, and reveals for the first time that SNHG1 regulates osteogenic differentiation by affecting pyroptosis.
Insights
This study reveals that SNHG1 suppresses bone formation in osteoporosis by activating pyroptosis via HMGB1 interaction. Targeting SNHG1 may offer a novel therapeutic strategy for osteoporosis treatment.
Area of Science:
- Biomedical Research
- Molecular Biology
- Cell Biology
Background:
- Osteoporosis (OP) poses a significant health burden on the elderly, with current treatments having limited long-term efficacy.
- Identifying novel therapeutic targets for OP is crucial for improving patient outcomes.
Purpose of the Study:
- To investigate the role of SNHG1 in osteogenic differentiation and its potential as a therapeutic target for osteoporosis.
- To elucidate the molecular mechanisms underlying SNHG1's function in bone metabolism.
Main Methods:
- Quantitative real-time PCR (RT-qPCR) and Western blotting to measure gene and protein expression.
- Enzyme-linked immunosorbent assay (ELISA) for cytokine detection.
- RNA pull-down assay to confirm molecular interactions.
- Alizarin red staining to assess osteogenic differentiation.
Main Results:
- SNHG1 and HMGB1 were upregulated in osteoporosis patients' serum and inhibited osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs).
- SNHG1 promotes HMGB1 expression, activates pyroptosis, and suppresses osteogenic differentiation.
- Silencing HMGB1 or inhibiting caspase-1 partially reversed SNHG1's inhibitory effects on osteogenesis.
Conclusions:
- SNHG1 suppresses osteogenic differentiation by activating pyroptosis through interaction with and promotion of HMGB1 expression.
- SNHG1 represents a potential therapeutic target for osteoporosis.
- This study reveals SNHG1's novel role in regulating osteogenic differentiation via pyroptosis.
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