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Inhibition of Protein Disulfide Isomerase Attenuates Osteoclast Differentiation and Function via the Readjustment of Cellular Redox State in Postmenopausal Osteoporosis

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Abstract

Due to the accumulation of reactive oxygen species (ROS) and heightened activity of osteoclasts, postmenopausal osteoporosis could cause severe pathological bone destruction. Protein disulfide isomerase (PDI), an endoplasmic prototypic thiol isomerase, plays a central role in affecting cellular redox state. To test whether suppression of PDI could inhibit osteoclastogenesis through cellular redox regulation, bioinformatics network analysis was performed on the causative genes, followed by biological validation on the osteoclastogenesis in vitro and ovariectomy (OVX) mice model in vivo. The analysis identified PDI as one of gene targets for postmenopausal osteoporosis, which was positively expressed during osteoclastogenesis. Therefore, PDI expression inhibitor and chaperone activity inhibitor were used to verify the effects of PDI inhibitors on osteoclastogenesis. Results demonstrated that PDI inhibitors could reduce osteoclast number and inhibit resorption function via suppression on osteoclast marker genes. The mechanisms behind the scenes were the PDI inhibitors-caused intracellular ROS reduction via enhancement of the antioxidant system. Micro-CT and histological results indicated PDI inhibitors could effectively alleviate or even prevent bone loss in OVX mice. In conclusion, our findings unveiled the suppressive effects of PDI inhibitors on osteoclastogenesis by reducing intracellular ROS, providing new therapeutic options for postmenopausal osteoporosis.

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The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

References

  1. Compston, J.E., M.R. McClung, and W.D. Leslie. 2019. Osteoporosis. Lancet (London, England) 393: 364–376.

    Article  CAS  PubMed  Google Scholar 

  2. Arceo-Mendoza, R.M., and P.M. Camacho. 2021. Postmenopausal osteoporosis: Latest guidelines. Endocrinology and metabolism clinics of North America 50: 167–178.

    Article  PubMed  Google Scholar 

  3. Wang, H., G. Yang, Y. Xiao, G. Luo, G. Li, and Z. Li. 2020. Friend or foe? Essential roles of osteoclast in maintaining skeletal health. BioMed research international 2020: 4791786.

    PubMed  PubMed Central  Google Scholar 

  4. Boyle, W.J., W.S. Simonet, and D.L. Lacey. 2003. Osteoclast differentiation and activation. Nature 423: 337–342.

    Article  CAS  PubMed  Google Scholar 

  5. Mohamad, N.V., S. Ima-Nirwana, and K.Y. Chin. 2020. Are Oxidative stress and inflammation mediators of bone loss due to estrogen deficiency? a review of current evidence. Endocrine, metabolic & immune disorders drug targets 20: 1478–1487.

    Article  CAS  Google Scholar 

  6. Cervellati, C., and C.M. Bergamini. 2016. Oxidative damage and the pathogenesis of menopause related disturbances and diseases. Clinical chemistry and laboratory medicine 54: 739–753.

    Article  CAS  PubMed  Google Scholar 

  7. Agidigbi, T. S., and C. Kim. 2019. Reactive oxygen species in osteoclast differentiation and possible pharmaceutical targets of ROS-mediated osteoclast diseases. International journal of molecular sciences 20.

  8. Kang, I.S., and C. Kim. 2016. NADPH oxidase gp91(phox) contributes to RANKL-induced osteoclast differentiation by upregulating NFATc1. Scientific reports 6: 38014.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Sies, H., and D.P. Jones. 2020. Reactive oxygen species (ROS) as pleiotropic physiological signalling agents. Nature reviews Molecular cell biology 21: 363–383.

    Article  CAS  PubMed  Google Scholar 

  10. Ng, A., Y. H., Z. Li, M. M. Jones, S. Yang, C. Li, C. Fu, et al. 2019. Regulator of G protein signaling 12 enhances osteoclastogenesis by suppressing Nrf2-dependent antioxidant proteins to promote the generation of reactive oxygen species. eLife 8.

  11. Kanzaki, H., F. Shinohara, I. Kanako, Y. Yamaguchi, S. Fukaya, Y. Miyamoto, et al. 2016. Molecular regulatory mechanisms of osteoclastogenesis through cytoprotective enzymes. Redox biology 8: 186–191.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Yan, G., Y. Guo, J. Guo, Q. Wang, C. Wang, and X. Wang. 2020. N-acetylcysteine attenuates lipopolysaccharide-induced osteolysis by restoring bone remodeling balance via reduction of reactive oxygen species formation during osteoclastogenesis. Inflammation 43: 1279–1292.

    Article  PubMed  Google Scholar 

  13. Chen, K., P. Qiu, Y. Yuan, L. Zheng, J. He, C. Wang, et al. 2019. Pseurotin A inhibits osteoclastogenesis and prevents ovariectomized-induced bone loss by suppressing reactive oxygen species. Theranostics 9: 1634–1650.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Zeeshan, H.M., G.H. Lee, H.R. Kim, and H.J. Chae. 2016. Endoplasmic reticulum stress and associated ROS. International journal of molecular sciences 17: 327.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Wang, L., X. Wang, and C.C. Wang. 2015. Protein disulfide-isomerase, a folding catalyst and a redox-regulated chaperone. Free radical biology & medicine 83: 305–313.

    Article  CAS  Google Scholar 

  16. Shergalis, A.G., S. Hu, A. Bankhead 3rd., and N. Neamati. 2020. Role of the ERO1-PDI interaction in oxidative protein folding and disease. Pharmacology & therapeutics 210: 107525.

    Article  CAS  Google Scholar 

  17. Zhang, Z., L. Zhang, L. Zhou, Y. Lei, Y. Zhang, and C. Huang. 2019. Redox signaling and unfolded protein response coordinate cell fate decisions under ER stress. Redox biology 25: 101047.

    Article  CAS  PubMed  Google Scholar 

  18. Xiong, B., V. Jha, J.K. Min, and J. Cho. 2020. Protein disulfide isomerase in cardiovascular disease. Experimental & molecular medicine 52: 390–399.

    Article  CAS  Google Scholar 

  19. Xu, X., J. Chiu, S. Chen, and C. Fang. 2021. Pathophysiological roles of cell surface and extracellular protein disulfide isomerase and their molecular mechanisms. British journal of pharmacology 178: 2911–2930.

    Article  CAS  PubMed  Google Scholar 

  20. Wang, L., and C. C. Wang. 2022. Oxidative protein folding fidelity and redoxtasis in the endoplasmic reticulum. Trends in biochemical sciences.

  21. Powell, L.E., and P.A. Foster. 2021. Protein disulphide isomerase inhibition as a potential cancer therapeutic strategy. Cancer medicine 10: 2812–2825.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Khan, M.M., S. Simizu, M. Kawatani, and H. Osada. 2011. The potential of protein disulfide isomerase as a therapeutic drug target. Oncology research 19: 445–453.

    Article  PubMed  Google Scholar 

  23. Wang, Y., A. Nizkorodov, K. Riemenschneider, C.S. Lee, R. Olivares-Navarrete, Z. Schwartz, et al. 2014. Impaired bone formation in Pdia3 deficient mice. PLoS ONE 9: e112708.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Hino, S., S. Kondo, K. Yoshinaga, A. Saito, T. Murakami, S. Kanemoto, et al. 2010. Regulation of ER molecular chaperone prevents bone loss in a murine model for osteoporosis. Journal of bone and mineral metabolism 28: 131–138.

    Article  CAS  PubMed  Google Scholar 

  25. Xiao, Y., C. Li, M. Gu, H. Wang, W. Chen, G. Luo, et al. 2018. Protein disulfide isomerase silence inhibits inflammatory functions of macrophages by suppressing reactive oxygen species and NF-κB pathway. Inflammation 41: 614–625.

    Article  CAS  PubMed  Google Scholar 

  26. Safran, M., N. Rosen, M. Twik, R. BarShir, T.I. Stein, D. Dahary, et al. 2021. The GeneCards Suite. In Practical Guide to Life Science Databases, ed. I. Abugessaisa and T. Kasukawa, 27–56. Singapore: Springer Nature Singapore.

    Chapter  Google Scholar 

  27. Davis, A.P., C.J. Grondin, R.J. Johnson, D. Sciaky, J. Wiegers, T.C. Wiegers, et al. 2021. Comparative toxicogenomics database (CTD): Update 2021. Nucleic acids research 49: D1138-d1143.

    Article  CAS  PubMed  Google Scholar 

  28. Uhlén, M., L. Fagerberg, B. M. Hallström, C. Lindskog, P. Oksvold, A. Mardinoglu, et al. 2015. Proteomics. Tissue-based map of the human proteome. Science. 347:1260419.

  29. Bardou, P., J. Mariette, F. Escudié, C. Djemiel, and C. Klopp. 2014. jvenn: An interactive Venn diagram viewer. BMC Bioinformatics 15: 293.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Szklarczyk, D., A.L. Gable, K.C. Nastou, D. Lyon, R. Kirsch, S. Pyysalo, et al. 2021. The STRING database in 2021: Customizable protein-protein networks, and functional characterization of user-uploaded gene/measurement sets. Nucleic acids research 49: D605-d612.

    Article  CAS  PubMed  Google Scholar 

  31. Li, Z., C. Li, Y. Zhou, W. Chen, G. Luo, Z. Zhang, et al. 2016. Advanced glycation end products biphasically modulate bone resorption in osteoclast-like cells. American journal of physiology Endocrinology and metabolism 310: E355–E366.

    Article  PubMed  Google Scholar 

  32. Chen, J., Z. Cui, Y. Wang, L. Lyu, C. Feng, D. Feng, et al. 2022. Cyclic polypeptide D7 protects bone marrow mesenchymal cells and promotes chondrogenesis during osteonecrosis of the femoral head via growth differentiation factor 15-mediated redox signaling. Oxidative medicine and cellular longevity 2022: 3182368.

    PubMed  PubMed Central  Google Scholar 

  33. Li, Z., T. Liu, A. Gilmore, N.M. Gómez, C. Fu, J. Lim, et al. 2019. Regulator of G protein signaling protein 12 (Rgs12) controls mouse osteoblast differentiation via calcium channel/oscillation and Gαi-ERK signaling. Journal of bone and mineral research : The official journal of the American Society for Bone and Mineral Research 34: 752–764.

    Article  CAS  PubMed  Google Scholar 

  34. Li, D., J. Liu, B. Guo, C. Liang, L. Dang, C. Lu, et al. 2016. Osteoclast-derived exosomal miR-214-3p inhibits osteoblastic bone formation. Nature communications 7: 10872.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Bouxsein, M.L., S.K. Boyd, B.A. Christiansen, R.E. Guldberg, K.J. Jepsen, and R. Müller. 2010. Guidelines for assessment of bone microstructure in rodents using micro-computed tomography. Journal of bone and mineral research : The official journal of the American Society for Bone and Mineral Research 25: 1468–1486.

    Article  PubMed  Google Scholar 

  36. Cheng, H., Z. Zheng, and T. Cheng. 2020. New paradigms on hematopoietic stem cell differentiation. Protein & cell 11: 34–44.

    Article  Google Scholar 

  37. Laurindo, F.R., L.A. Pescatore, and Dde C. Fernandes. 2012. Protein disulfide isomerase in redox cell signaling and homeostasis. Free radical biology & medicine 52: 1954–1969.

    Article  CAS  Google Scholar 

  38. Jha, V., T. Kumari, V. Manickam, Z. Assar, K.L. Olson, J.K. Min, et al. 2021. ERO1-PDI Redox signaling in health and disease. Antioxidants & redox signaling 35: 1093–1115.

    Article  CAS  Google Scholar 

  39. Ping, S., S. Liu, Y. Zhou, Z. Li, Y. Li, K. Liu, et al. 2017. Protein disulfide isomerase-mediated apoptosis and proliferation of vascular smooth muscle cells induced by mechanical stress and advanced glycosylation end products result in diabetic mouse vein graft atherosclerosis. Cell death & disease 8: e2818.

    Article  CAS  Google Scholar 

  40. Linz, A., Y. Knieper, T. Gronau, U. Hansen, A. Aszodi, N. Garbi, et al. 2015. ER Stress during the pubertal growth spurt results in impaired long-bone growth in chondrocyte-specific ERp57 knockout mice. Journal of bone and mineral research : The official journal of the American Society for Bone and Mineral Research 30: 1481–1493.

    Article  CAS  PubMed  Google Scholar 

  41. Da, W., L. Tao, and Y. Zhu. 2021. The role of osteoclast energy metabolism in the occurrence and development of osteoporosis. Front Endocrinol (Lausanne) 12: 675385.

    Article  PubMed  Google Scholar 

  42. Meng, Q., Y. Wang, T. Yuan, Y. Su, Z. Li, and S. Sun. 2023. Osteoclast: The novel whistleblower in osteonecrosis of the femoral head. Gene Reports 33: 101833.

    Article  CAS  Google Scholar 

  43. Cong, Y., Y. Wang, T. Yuan, Z. Zhang, J. Ge, Q. Meng, et al. 2023. Macrophages in aseptic loosening: Characteristics, functions, and mechanisms. Frontiers in immunology 14: 1122057.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Huang, W., Y. Gong, L. Yan. 2023. ER Stress, the unfolded protein response and osteoclastogenesis: a review. Biomolecules. 13.

  45. Wang, K., J. Niu, H. Kim, and P.E. Kolattukudy. 2011. Osteoclast precursor differentiation by MCPIP via oxidative stress, endoplasmic reticulum stress, and autophagy. Journal of Molecular Cell Biology 3: 360–368.

    Article  PubMed  PubMed Central  Google Scholar 

  46. Wen, Z., Q. Sun, Y. Shan, W. Xie, Y. Ding, W. Wang, et al. 2023. Endoplasmic reticulum stress in osteoarthritis: A novel perspective on the pathogenesis and treatment. Aging & Disease 14: 283–286.

    Google Scholar 

  47. He, M., D. Li, C. Fang, and Q. Xu. 2022. YTHDF1 regulates endoplasmic reticulum stress, NF-kappaB, MAPK and PI3K-AKT signaling pathways in inflammatory osteoclastogenesis. Archives of Biochemistry and Biophysics 732: 109464.

    Article  CAS  PubMed  Google Scholar 

  48. Victor, P., D. Sarada, and K.M. Ramkumar. 2021. Crosstalk between endoplasmic reticulum stress and oxidative stress: Focus on protein disulfide isomerase and endoplasmic reticulum oxidase 1. European journal of pharmacology 892: 173749.

    Article  CAS  PubMed  Google Scholar 

  49. Nomura, J., T. Hosoi, M. Kaneko, K. Ozawa, A. Nishi, Y. Nomura. 2016. Neuroprotection by endoplasmic reticulum stress-induced HRD1 and chaperones: possible therapeutic targets for Alzheimer's and Parkinson's disease. Medical Science (Basel). 4.

  50. Hurst, K. E., K. A. Lawrence, L. Reyes Angeles, Z. Ye, J. Zhang, D. M. Townsend, et al. 2019. Endoplasmic reticulum protein disulfide isomerase shapes T cell efficacy for adoptive cellular therapy of tumors. Cells. 8.

  51. Li, X., Y. Li, R. Wang, Q. Wang, L. Lu. 2019. Toxoflavin produced by Burkholderia gladioli from Lycoris aurea is a new broad-spectrum fungicide. Applied and environmental microbiology. 85.

  52. Kyani, A., S. Tamura, S. Yang, A. Shergalis, S. Samanta, Y. Kuang, et al. 2018. Discovery and mechanistic elucidation of a class of protein disulfide isomerase inhibitors for the treatment of glioblastoma. ChemMedChem 13: 164–177.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Horibe, T., H. Nagai, K. Sakakibara, Y. Hagiwara, and M. Kikuchi. 2001. Ribostamycin inhibits the chaperone activity of protein disulfide isomerase. Biochemical and biophysical research communications 289: 967–972.

    Article  CAS  PubMed  Google Scholar 

  54. Ko, M.K., and E.P. Kay. 2004. PDI-mediated ER retention and proteasomal degradation of procollagen I in corneal endothelial cells. Experimental cell research 295: 25–35.

    Article  CAS  PubMed  Google Scholar 

  55. Veis, D. J., and C. A. O'Brien. 2022. Osteoclasts, Master Sculptors of Bone. Annual review of pathology.

  56. Blangy, A., G. Bompard, D. Guerit, P. Marie, J. Maurin, A. Morel, et al. 2020. The osteoclast cytoskeleton - current understanding and therapeutic perspectives for osteoporosis. Journal of cell science. 133.

  57. Xin, Y., Y. Liu, D. Liu, J. Li, C. Zhang, Y. Wang, et al. 2020. New function of RUNX2 in regulating osteoclast differentiation via the AKT/NFATc1/CTSK Axis. Calcified tissue international 106: 553–566.

    Article  CAS  PubMed  Google Scholar 

  58. Zeng, X.Z., Y.Y. Zhang, Q. Yang, S. Wang, B.H. Zou, Y.H. Tan, et al. 2020. Artesunate attenuates LPS-induced osteoclastogenesis by suppressing TLR4/TRAF6 and PLCγ1-Ca(2+)-NFATc1 signaling pathway. Acta pharmacologica Sinica 41: 229–236.

    Article  CAS  PubMed  Google Scholar 

  59. Rao, A., C. Luo, and P.G. Hogan. 1997. Transcription factors of the NFAT family: Regulation and function. Annual review of immunology 15: 707–747.

    Article  CAS  PubMed  Google Scholar 

  60. Yuan, X., J. Cao, T. Liu, Y.P. Li, F. Scannapieco, X. He, et al. 2015. Regulators of G protein signaling 12 promotes osteoclastogenesis in bone remodeling and pathological bone loss. Cell death and differentiation 22: 2046–2057.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Feno, S., G. Butera, D. Vecellio Reane, R. Rizzuto, and A. Raffaello. 2019. Crosstalk between calcium and ROS in pathophysiological conditions. Oxidative medicine and cellular longevity 2019: 9324018.

    Article  PubMed  PubMed Central  Google Scholar 

  62. Kovac, S., P.R. Angelova, K.M. Holmström, Y. Zhang, A.T. Dinkova-Kostova, and A.Y. Abramov. 2015. Nrf2 regulates ROS production by mitochondria and NADPH oxidase. Biochimica et biophysica acta 1850: 794–801.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Lu, J., and A. Holmgren. 2014. The thioredoxin antioxidant system. Free Radical Biology & Medicine 66: 75–87.

    Article  CAS  Google Scholar 

  64. Ferreira de Oliveira, J. M., M. Costa, T. Pedrosa, P. Pinto, C. Remedios, H. Oliveira, et al. 2014. Sulforaphane induces oxidative stress and death by p53-independent mechanism: implication of impaired glutathione recycling. PLoS One. 9:e92980.

  65. Hu, Y., S. Urig, S. Koncarevic, X. Wu, M. Fischer, S. Rahlfs, et al. 2007. Glutathione- and thioredoxin-related enzymes are modulated by sulfur-containing chemopreventive agents. Biological Chemistry 388: 1069–1081.

    Article  CAS  PubMed  Google Scholar 

  66. Li, Z.Q., and C.H. Li. 2020. CRISPR/Cas9 from bench to bedside: What clinicians need to know before application? Military Medical Research 7: 61.

    Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

This research was funded by National Natural Science Foundation of China (nos. 82100936 and 81972056), Natural Science Foundation of Shandong Province (no. ZR2021QH077), and Taishan Scholar Foundation of Shandong Province (no. tsqnz20221170). Drafts of Figs. 8 and 9 were created with BioRender.com.

Funding

National Natural Science Foundation of China,82100936,81972056,Natural Science Foundation of Shandong Province,ZR2021QH077,Taishan Scholar Foundation of Shandong Province,tsqnz20221170

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Author notes

  1. Yi Wang and Tao Yuan contributed equally to this work.

Authors and Affiliations

  1. Department of Joint Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, 250021, Shandong, China

    Yi Wang, Changgong Feng, Ziqing Li & Shui Sun

  2. Department of Joint Surgery, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250012, Shandong, China

    Tao Yuan, Haojue Wang, Qi Meng, Haoyang Li & Shui Sun

  3. Orthopaedic Research Laboratory, Medical Science and Technology Innovation Center, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, 250117, Shandong, China

    Yi Wang, Changgong Feng, Ziqing Li & Shui Sun

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  1. Yi Wang
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Contributions

All authors contributed to the study conception and design. YW and TY conceived the experiments, analyzed data, and wrote the manuscript. HJW and HYL collected data from databases and performed bioinformatics analysis. QM and CGF participated in the experiments. ZQL and SS designed experiments and polished the manuscript. All authors approved the final version.

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Correspondence to Ziqing Li or Shui Sun.

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All experiments involving mice were performed following the protocol approved by the Institutional Animal Care and Use Committee (IACUC) of the Shandong Provincial Hospital Affiliated to Shandong First Medical University (Shandong, China; NSFC: no. 2021–038).

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Supplementary Information

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10753_2023_1933_MOESM1_ESM.xlsx

Supplementary file1: Top 1500 genes retrieved from the GeneCards using “osteoporosis”, “osteoclast”, “estrogen”, “fracture” and “oxidative stress” as keywords. (XLSX 91 KB)

10753_2023_1933_MOESM2_ESM.xlsx

Supplementary file2: Top 100 associated gene targets of drugs retrieved from the CTD using “osteoporosis” as the keyword. (XLSX 14 KB)

Supplementary file3: 165 overlapping genes from the GeneCards. (XLSX 14 KB)

Supplementary file4: 33 therapeutic gene targets of osteoporosis. (XLSX 12 KB)

Supplementary file5: Cytotoxicity of different concentrations of PDI inhibitors on BMMs. (DOCX 171 KB)

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Wang, Y., Yuan, T., Wang, H. et al. Inhibition of Protein Disulfide Isomerase Attenuates Osteoclast Differentiation and Function via the Readjustment of Cellular Redox State in Postmenopausal Osteoporosis. Inflammation 47, 626–648 (2024). https://doi.org/10.1007/s10753-023-01933-z

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