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Long Non-coding RNA SNHG1 Suppresses the Osteogenic Differentiation of Bone Marrow Mesenchymal Stem Cells by Binding with HMGB1

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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.

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Data Availability

The data underlying this article will be shared on reasonable request to the corresponding author.

Abbreviations

ALP:

Alkaline phosphatase

BMNCR:

Bone marrow associated non-coding RNA

BMSCs:

Bone marrow mesenchymal stem cells

CASC11:

Cancer susceptibility 11

CRNDE:

Colorectal neoplasia differentially expressed

DANCR:

Differentiation antagonizing nonprotein coding RNA

GAS5:

Growth arrest-specific 5

GSDMD:

Gasdermin D

HMGB1:

High-mobility group box chromosomal protein-1

lncRNAs:

Long non-coding RNAs

OCN:

Osteocalcin

OPN:

Osteopontin

OP:

Osteoporosis

SNHG1:

Small nucleolar RNA host gene 1

References

  • Aibar-Almazán A, Voltes-Martínez A, Castellote-Caballero Y (2022) Current status of the diagnosis and management of osteoporosis. Int J Mol Sci 23(16):9465

    Article  PubMed  PubMed Central  Google Scholar 

  • Burdette BE, Esparza AN, Zhu H, Wang S (2021) Gasdermin D in pyroptosis. Acta Pharm Sin B 11:2768–2782

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chen G, Ward MF, Sama AE, Wang H (2004) Extracellular HMGB1 as a proinflammatory cytokine. J Interferon Cytokine Res 24:329–333

    Article  PubMed  Google Scholar 

  • Chen R, Kang R, Tang D (2022) The mechanism of HMGB1 secretion and release. Exp Mol Med 54:91–102

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chen H, Zheng Q, Lv Y, Yang Z, Fu Q (2023) CUL4A-mediated ZEB1/microRNA-340-5p/HMGB1 axis promotes the development of osteoporosis. J Biochem Mol Toxicol 37:e23373

    Article  CAS  PubMed  Google Scholar 

  • Fang Y, Tian S, Pan Y, Li W, Wang Q, Tang Y et al (2020) Pyroptosis: a new frontier in cancer. Biomed Pharmacother 121:109595

    Article  CAS  PubMed  Google Scholar 

  • Feng L, Xue D, Chen E, Zhang W, Gao X, Yu J et al (2016) HMGB1 promotes the secretion of multiple cytokines and potentiates the osteogenic differentiation of mesenchymal stem cells through the Ras/MAPK signaling pathway. Exp Ther Med 12:3941–3947

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fischer V, Haffner-Luntzer M (2022) Interaction between bone and immune cells: implications for postmenopausal osteoporosis. Semin Cell Dev Biol 123:14–21

    Article  PubMed  Google Scholar 

  • Fu Y, Hu X, Gao Y, Li K, Fu Q, Liu Q et al (2021) LncRNA ROR/miR-145-5p axis modulates the osteoblasts proliferation and apoptosis in osteoporosis. Bioengineered 12:7714–7723

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • He F, Bai J, Wang J, Zhai J, Tong L (2019) Irradiation-induced osteocyte damage promotes HMGB1-mediated osteoclastogenesis in vitro. J Cell Physiol 234:17314–17325

    Article  CAS  PubMed  Google Scholar 

  • Hu C, Li J, Tan Y, Liu Y, Bai C, Gao J et al (2022) Tanreqing injection attenuates macrophage activation and the inflammatory response via the lncRNA-SNHG1/HMGB1 axis in lipopolysaccharide-induced acute lung injury. Front Immunol 13:820718

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jiang Y, Wu W, Jiao G, Chen Y, Liu H (2019) LncRNA SNHG1 modulates p38 MAPK pathway through Nedd4 and thus inhibits osteogenic differentiation of bone marrow mesenchymal stem cells. Life Sci 228:208–214

    Article  CAS  PubMed  Google Scholar 

  • Johnston CB, Dagar M (2020) Osteoporosis in older adults. Med Clin N Am 104:873–884

    Article  PubMed  Google Scholar 

  • Ko NY, Chen LR, Chen KH (2020) The role of micro RNA and long-non-coding RNA in osteoporosis. J Mol Sci 21(14):4886

    Article  CAS  Google Scholar 

  • Li M, Zheng H, Han Y, Chen Y, Li B, Chen G et al (2021) LncRNA Snhg1-driven self-reinforcing regulatory network promoted cardiac regeneration and repair after myocardial infarction. Theranostics 11:9397–9414

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • McKenzie BA, Mamik MK, Saito LB, Boghozian R, Monaco MC, Major EO et al (2018) Caspase-1 inhibition prevents glial inflammasome activation and pyroptosis in models of multiple sclerosis. Proc Natl Acad Sci USA 115:E6065-e6074

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Muñoz J, Akhavan NS, Mullins AP, Arjmandi BH (2020) Macrophage polarization and osteoporosis: a review. Nutrients 12(10):2999

    Article  PubMed  PubMed Central  Google Scholar 

  • Reginster JY, Neuprez A, Dardenne N, Beaudart C, Emonts P, Bruyere O (2014) Efficacy and safety of currently marketed anti-osteoporosis medications. Best Pract Res Clin Endocrinol Metab 28:809–834

    Article  CAS  PubMed  Google Scholar 

  • Shi J, Gao W, Shao F (2017) Pyroptosis: gasdermin-mediated programmed necrotic cell death. Trends Biochem Sci 42:245–254

    Article  CAS  PubMed  Google Scholar 

  • Sun Q, Gong J, Wu J, Hu Z, Zhang Q, Zhu X (2022) SNHG1-miR-186-5p-YY1 feedback loop alleviates hepatic ischemia/reperfusion injury. Cell Cycle 21:1267–1279

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tan X, Chen WB, Lv DJ, Yang TW, Wu KH, Zou LB et al (2021) LncRNA SNHG1 and RNA binding protein hnRNPL form a complex and coregulate CDH1 to boost the growth and metastasis of prostate cancer. Cell Death Dis 12:138

    Article  PubMed  PubMed Central  Google Scholar 

  • Tao Z, Wang J, Wen K, Yao R, Da W, Zhou S et al (2020) Pyroptosis in osteoblasts: a novel hypothesis underlying the pathogenesis of osteoporosis. Front Endocrinol (lausanne) 11:548812

    Article  PubMed  Google Scholar 

  • Tao H, Li W, Zhang W, Yang C, Zhang C, Liang X et al (2021) Urolithin A suppresses RANKL-induced osteoclastogenesis and postmenopausal osteoporosis by, suppresses inflammation and downstream NF-κB activated pyroptosis pathways. Pharmacol Res 174:105967

    Article  CAS  PubMed  Google Scholar 

  • Wang Y, Zhang H (2020) TNF-α/HMGB1 inflammation signalling pathway regulates pyroptosis during liver failure and acute kidney injury. Cell Prolif 53:12829

    Article  Google Scholar 

  • Wang Q, Li Y, Zhang Y, Ma L, Lin L, Meng J et al (2017) LncRNA MEG3 inhibited osteogenic differentiation of bone marrow mesenchymal stem cells from postmenopausal osteoporosis by targeting miR-133a-3p. Biomed Pharmacother 89:1178–1186

    Article  CAS  PubMed  Google Scholar 

  • Wang CG, Hu YH, Su SL, Zhong D (2020) LncRNA DANCR and miR-320a suppressed osteogenic differentiation in osteoporosis by directly inhibiting the Wnt/β-catenin signaling pathway. Exp Mol Med 52:1310–1325

    Article  PubMed  PubMed Central  Google Scholar 

  • Wu D, Cline-Smith A, Shashkova E, Perla A, Katyal A, Aurora R (2021) T-cell mediated inflammation in postmenopausal osteoporosis. Front Immunol 12:687551

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Xiang J, Fu HQ, Xu Z, Fan WJ, Liu F, Chen B (2020) lncRNA SNHG1 attenuates osteogenic differentiation via the miR-101/DKK1 axis in bone marrow mesenchymal stem cells. Mol Med Rep 22:3715–3722

    CAS  PubMed  PubMed Central  Google Scholar 

  • Xu M, Chen X, Lin K, Zeng K, Liu X, Pan B et al (2018a) The long noncoding RNA SNHG1 regulates colorectal cancer cell growth through interactions with EZH2 and miR-154–5p. Mol Cancer 17:141

    Article  PubMed  PubMed Central  Google Scholar 

  • Xu YJ, Zheng L, Hu YW, Wang Q (2018b) Pyroptosis and its relationship to atherosclerosis. Clin Chim Acta 476:28–37

    Article  CAS  PubMed  Google Scholar 

  • Yang X, Jiang T, Wang Y, Guo L (2019) The role and mechanism of SIRT1 in resveratrol-regulated osteoblast autophagy in osteoporosis rats. Sci Rep 9:18424

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yang Y, Yujiao W, Fang W, Linhui Y, Ziqi G, Zhichen W et al (2020) The roles of miRNA, lncRNA and circRNA in the development of osteoporosis. Biol Res 53:40

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yu X, Rong PZ, Song MS, Shi ZW, Feng G, Chen XJ et al (2021) lncRNA SNHG1 induced by SP1 regulates bone remodeling and angiogenesis via sponging miR-181c-5p and modulating SFRP1/Wnt signaling pathway. Mol Med 27:141

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yu H, Zhou W, Zhong Z, Qiu R, Chen G, Zhang P (2022) High-mobility group box chromosomal protein-1 deletion alleviates osteoporosis in OVX rat model via suppressing the osteoclastogenesis and inflammation. J Interferon Cytokine Res 17:232

    Google Scholar 

  • Zhang L, Zheng YL, Wang R, Wang XQ, Zhang H (2022) Exercise for osteoporosis: a literature review of pathology and mechanism. Front Immunol 13:1005665

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang L, Xu L, Wang Y, Zhang X, Xue T, Sun Q et al (2023) Histone methyltransferase Setdb1 mediates osteogenic differentiation by suppressing the expression of miR-212-3p under mechanical unloading. Cell Signal 102:110554

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

We would like to give our sincere gratitude to the reviewers for their constructive comments.

Funding

This work was supported by Changsha Natural Science Foundation (No. kq2202006).

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Authors and Affiliations

  1. Department of Orthopaedics, The First Hospital of Changsha, No. 311, Yingpan Road, Kaifu District, Changsha, 410005, Hunan, People’s Republic of China

    Kaihua Pan, Yuanyuan Lu, Daning Cao, Jiang Peng, Yunqing Zhang & Xiaoming Li

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  1. Kaihua Pan
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  2. Yuanyuan Lu
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  3. Daning Cao
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  4. Jiang Peng
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  5. Yunqing Zhang
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  6. Xiaoming Li
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Contributions

Conception and design of study: XL. Acquisition of data: KP; DC; YZ. Analysis and interpretation of data: YL; JP. Drafting the manuscript: KP. Revising the manuscript critically for important intellectual content: XL.

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Correspondence to Xiaoming Li.

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Ethical Approval

This study has obtained approval of the Ethics Committee of The First Hospital of Changsha (No. 2022-6) and the patient’s written informed consent.

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All participants were informed and gave written consent.

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Supplementary Information

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10528_2023_10564_MOESM1_ESM.tif

Supplementary file1 (TIF 47954 kb) Supplementary figure 1. Detection of the interference efficiency of HMGB1 siRNA and VX765. (A-C) Three different sequences of HMGB1 siRNAs were transfected into BMSCs. Then, the expression of HMGB1 mRNA was determined by RT-qPCR, and the expression of HMGB1 protein was determined by Western blotting assay. (D and E) BMSCs were treated with 0, 30, 40, and 50 μM of VX765. The expression of caspase-1 p20 was measured by Western blotting assay. *P < 0.05, **P < 0.01, and ***P < 0.001.

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Pan, K., Lu, Y., Cao, D. et al. Long Non-coding RNA SNHG1 Suppresses the Osteogenic Differentiation of Bone Marrow Mesenchymal Stem Cells by Binding with HMGB1. Biochem Genet (2023). https://doi.org/10.1007/s10528-023-10564-w

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