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Cited by 11Orthopaedic implants and arthroplastyInflammasome and immune disordersOrthopedic Infections and Treatments

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Desferrioxamine alleviates UHMWPE particle-induced osteoclastic osteolysis by inhibiting caspase-1-dependent pyroptosis in osteocytes

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Zhao, Shenli, Ge, Chen, Li, Yao, Chang, Leilei, Dan, Zhou, Tu, Yihui, Deng, Lianfu, Kang, Hui, Li, Changwei·2022·Journal of Biological Engineering
DOI 10.1186/s13036-022-00314-8PMC PMC9733322
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Abstract

Background: Cell death and inflammation are the two important triggers of wear particle-induced osteolysis. Particles, including cobalt-chromium-molybdenum and tricalcium phosphate, have been reported to induce pyroptosis in macrophages and osteocytes. Although macrophage pyroptosis facilitates osteoclastic bone resorption and osteolysis, whether osteocyte pyroptosis is involved in osteoclastic osteolysis still needs further investigation. Desferrioxamine (DFO), an FDA-approved medication and a powerful iron chelator, has been proven to reduce ultrahigh-molecular-weight polyethylene (UHMWPE) particle-induced osteolysis. However, whether DFO can ameliorate UHMWPE particle-induced osteolysis by decreasing pyroptosis in osteocytes is unknown. Results: A mouse calvarial osteolysis model and the mouse osteocyte cell line MLO-Y4 was used, and we found that pyroptosis in osteocytes was significantly induced by UHMWPE particles. Furthermore, our findings uncovered a role of caspase-1-dependent pyroptosis in osteocytes in facilitating osteoclastic osteolysis induced by UHMWPE particles. In addition, we found that DFO could alleviate UHMWPE particle-induced pyroptosis in osteocytes in vivo and in vitro. Conclusions: We uncovered a role of caspase-1-dependent pyroptosis in osteocytes in facilitating osteoclastic osteolysis induced by UHMWPE particles. Furthermore, we found that DFO alleviated UHMWPE particle-induced osteoclastic osteolysis partly by inhibiting pyroptosis in osteocytes. Graphical Abstract: Schematic of DFO reducing UHMWPE particle-induced osteolysis by inhibiting osteocytic pyroptosis. Wear particles, such as polymers, generated from prosthetic implant materials activate canonical inflammasomes and promote the cleavage and activation of caspase-1. This is followed by caspase-1-dependent IL-β maturation and GSDMD cleavage. The N-terminal fragment of GSDMD binds to phospholipids on the cell membrane and forms holes in the membrane, resulting in the release of mature IL-β and inflammatory intracellular contents. This further facilitates osteoclastic differentiation of BMMs, resulting in excessive bone resorption and ultimately leading to prosthetic osteolysis. DFO reduces UHMWPE particle-induced osteolysis by inhibiting osteocytic pyroptosis.

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Research works printed but not linked: 55

  1. Zhang Y, Yan M, Yu A, Mao H, Zhang J. Inhibitory effects of beta-tricalciumphosphate wear particles on osteocytes via apoptotic response and Akt inactivation. Toxicology. 2012;297(1–3):57–67. · DOI
  2. Grandjean-Laquerriere A, Laquerriere P, Guenounou M, Laurent-Maquin D, Phillips TM. Importance of the surface area ratio on cytokines production by human monocytes in vitro induced by various hydroxyapatite particles. Biomaterials. 2005;26(15):2361–9. · DOI
  3. Yang SY, Ren W, Park Y, Sieving A, Hsu S, Nasser S, et al. Diverse cellular and apoptotic responses to variant shapes of UHMWPE particles in a murine model of inflammation. Biomaterials. 2002;23(17):3535–43. · DOI
  4. Lange T, Schilling AF, Peters F, Haag F, Morlock MM, Rueger JM, et al. Proinflammatory and osteoclastogenic effects of beta-tricalciumphosphate and hydroxyapatite particles on human mononuclear cells in vitro. Biomaterials. 2009;30(29):5312–8. · DOI
  5. Yu B, Chang J, Liu Y, Li J, Kevork K, Al-Hezaimi K, et al. Wnt4 signaling prevents skeletal aging and inflammation by inhibiting nuclear factor-kappaB. Nat Med. 2014;20(9):1009–17. · DOI
  6. Horowitz MC, Lorenzo JA. The origins of osteoclasts. Curr Opin Rheumatol. 2004;16(4):464–8. · DOI
  7. Liu F, Zhu Z, Mao Y, Liu M, Tang T, Qiu S. Inhibition of titanium particle-induced osteoclastogenesis through inactivation of NFATc1 by VIVIT peptide. Biomaterials. 2009;30(9):1756–62. · DOI
  8. Greenfield EM, Bi Y, Ragab AA, Goldberg VM, Van De Motter RR. The role of osteoclast differentiation in aseptic loosening. J Orthop Res. 2002;20(1):1–8. · DOI
  9. Holt G, Murnaghan C, Reilly J, Meek RM. The biology of aseptic osteolysis. Clin Orthop Relat Res. 2007;460:240–52. · DOI
  10. Nakashima T, Hayashi M, Fukunaga T, Kurata K, Oh-Hora M, Feng JQ, et al. Evidence for osteocyte regulation of bone homeostasis through RANKL expression. Nat Med. 2011;17(10):1231–4. · DOI · Paper page
  11. Prideaux M, Findlay DM, Atkins GJ. Osteocytes: The master cells in bone remodelling. Curr Opin Pharmacol. 2016;28:24–30. · DOI
  12. Bonewald LF. Osteocytes as dynamic multifunctional cells. Ann N Y Acad Sci. 2007;1116:281–90. · DOI
  13. Chen K, Zhao J, Qiu M, Zhang L, Yang K, Chang L, et al. Osteocytic HIF-1alpha Pathway Manipulates Bone Micro-structure and Remodeling via Regulating Osteocyte Terminal Differentiation. Front Cell Dev Biol. 2021;9: 721561. · DOI
  14. Tatsumi S, Ishii K, Amizuka N, Li M, Kobayashi T, Kohno K, et al. Targeted ablation of osteocytes induces osteoporosis with defective mechanotransduction. Cell Metab. 2007;5(6):464–75. · DOI · Paper page
  15. Huber C, Collishaw S, Mosley JR, Reeve J, Noble BS. Selective estrogen receptor modulator inhibits osteocyte apoptosis during abrupt estrogen withdrawal: implications for bone quality maintenance. Calcif Tissue Int. 2007;81(2):139–44. · DOI
  16. Storlino G, Colaianni G, Sanesi L, Lippo L, Brunetti G, Errede M, et al. Irisin Prevents Disuse-Induced Osteocyte Apoptosis. J Bone Miner Res. 2020;35(4):766–75. · DOI
  17. Ormsby RT, Solomon LB, Yang D, Crotti TN, Haynes DR, Findlay DM, et al. Osteocytes respond to particles of clinically-relevant conventional and cross-linked polyethylene and metal alloys by up-regulation of resorptive and inflammatory pathways. Acta Biomater. 2019;87:296–306. · DOI
  18. Atkins GJ, Welldon KJ, Holding CA, Haynes DR, Howie DW, Findlay DM. The induction of a catabolic phenotype in human primary osteoblasts and osteocytes by polyethylene particles. Biomaterials. 2009;30(22):3672–81. · DOI
  19. Holding CA, Findlay DM, Stamenkov R, Neale SD, Lucas H, Dharmapatni AS, et al. The correlation of RANK, RANKL and TNFalpha expression with bone loss volume and polyethylene wear debris around hip implants. Biomaterials. 2006;27(30):5212–9. · DOI
  20. Gallo J, Raska M, Mrazek F, Petrek M. Bone remodeling, particle disease and individual susceptibility to periprosthetic osteolysis. Physiol Res. 2008;57(3):339–49. · DOI
  21. Zhang Y, Zou B, Tan Y, Su J, Wang Y, Xu J, et al. Sinomenine inhibits osteolysis in breast cancer by reducing IL-8/CXCR1 and c-Fos/NFATc1 signaling. Pharmacol Res. 2019;142:140–50. · DOI
  22. Wu H, Huang T, Ying L, Han C, Li D, Xu Y, et al. MiR-155 is Involved in Renal Ischemia-Reperfusion Injury via Direct Targeting of FoxO3a and Regulating Renal Tubular Cell Pyroptosis. Cell Physiol Biochem. 2016;40(6):1692–705. · DOI
  23. Nie H, Xue X, Li J, Liu X, Lv S, Guan G, et al. Nitro-oleic acid attenuates OGD/R-triggered apoptosis in renal tubular cells via inhibition of Bax mitochondrial translocation in a PPAR-gamma-dependent manner. Cell Physiol Biochem. 2015;35(3):1201–18. · DOI
  24. Dong T, Liao D, Liu X, Lei X. Using Small Molecules to Dissect Non-apoptotic Programmed Cell Death: Necroptosis, Ferroptosis, and Pyroptosis. ChemBioChem. 2015;16(18):2557–61. · DOI
  25. Croker BA, Silke J, Gerlic M. Fight or flight: regulation of emergency hematopoiesis by pyroptosis and necroptosis. Curr Opin Hematol. 2015;22(4):293–301. · DOI
  26. Yang Y, Jiang G, Zhang P, Fan J. Programmed cell death and its role in inflammation. Mil Med Res. 2015;2:12.
  27. Jorgensen I, Lopez JP, Laufer SA, Miao EA. IL-1beta, IL-18, and eicosanoids promote neutrophil recruitment to pore-induced intracellular traps following pyroptosis. Eur J Immunol. 2016;46(12):2761–6. · DOI
  28. Napier BA, Brubaker SW, Sweeney TE, Monette P, Rothmeier GH, Gertsvolf NA, et al. Complement pathway amplifies caspase-11-dependent cell death and endotoxin-induced sepsis severity. J Exp Med. 2016;213(11):2365–82. · DOI · Paper page
  29. Pillon NJ, Chan KL, Zhang S, Mejdani M, Jacobson MR, Ducos A, et al. Saturated fatty acids activate caspase-4/5 in human monocytes, triggering IL-1beta and IL-18 release. Am J Physiol Endocrinol Metab. 2016;311(5):E825–35. · DOI
  30. Xue S, Xu Y, Xu S, Zhong Y, Ruan G, Ma J, et al. Mitophagy impairment mediates the pathogenesis of CoCrMo particle-induced osteolysis via NLRP3/caspase-1/GSDMD-dependent pyroptosis in macrophages. Chem Eng J. 2022;435:135115. · DOI
  31. Zhang Y, Yan M, Niu W, Mao H, Yang P, Xu B, et al. Tricalcium phosphate particles promote pyroptotic death of calvaria osteocytes through the ROS/NLRP3/Caspase-1 signaling axis in amouse osteolysis model. Int Immunopharmacol. 2022;107: 108699. · DOI
  32. Wang Z, Liu N, Liu K, Zhou G, Gan J, Wang Z, et al. Autophagy mediated CoCrMo particle-induced peri-implant osteolysis by promoting osteoblast apoptosis. Autophagy. 2015;11(12):2358–69. · DOI
  33. Kandahari AM, Yang X, Laroche KA, Dighe AS, Pan D, Cui Q. A review of UHMWPE wear-induced osteolysis: the role for early detection of the immune response. Bone Res. 2016;4:16014. · DOI
  34. Prieto-Alhambra D, Javaid MK, Judge A, Murray D, Carr A, Cooper C, et al. Association between bisphosphonate use and implant survival after primary total arthroplasty of the knee or hip: population based retrospective cohort study. BMJ. 2011;343: d7222. · DOI
  35. Sellmeyer DE. Atypical fractures as a potential complication of long-term bisphosphonate therapy. JAMA. 2010;304(13):1480–4. · DOI
  36. Li YX, Ding SJ, Xiao L, Guo W, Zhan Q. Desferoxamine preconditioning protects against cerebral ischemia in rats by inducing expressions of hypoxia inducible factor 1 alpha and erythropoietin. Neurosci Bull. 2008;24(2):89–95. · DOI
  37. Jia P, Chen H, Kang H, Qi J, Zhao P, Jiang M, et al. Deferoxamine released from poly(lactic-co-glycolic acid) promotes healing of osteoporotic bone defect via enhanced angiogenesis and osteogenesis. J Biomed Mater Res A. 2016;104(10):2515–27. · DOI
  38. Guo JP, Pan JX, Xiong L, Xia WF, Cui S, Xiong WC. Iron Chelation Inhibits Osteoclastic Differentiation In Vitro and in Tg2576 Mouse Model of Alzheimer’s Disease. PLoS ONE. 2015;10(11): e0139395. · DOI
  39. Kang H, Yan Y, Jia P, Yang K, Guo C, Chen H, et al. Desferrioxamine reduces ultrahigh-molecular-weight polyethylene-induced osteolysis by restraining inflammatory osteoclastogenesis via heme oxygenase-1. Cell Death Dis. 2016;7(10): e2435. · DOI
  40. Li H, Li Y, Song C, Hu Y, Dai M, Liu B, et al. Neutrophil Extracellular Traps Augmented Alveolar Macrophage Pyroptosis via AIM2 Inflammasome Activation in LPS-Induced ALI/ARDS. J Inflamm Res. 2021;14:4839–58. · DOI
  41. Lohmann CH, Dean DD, Bonewald LF, Schwartz Z, Boyan BD. Nitric oxide and prostaglandin E2 production in response to ultra-high molecular weight polyethylene particles depends on osteoblast maturation state. J Bone Joint Surg Am. 2002;84-A(3):411–9. · DOI
  42. Magna M, Pisetsky DS. The Role of Cell Death in the Pathogenesis of SLE: Is Pyroptosis the Missing Link? Scand J Immunol. 2015;82(3):218–24. · DOI
  43. Zhao Y, Shao F. The NAIP-NLRC4 inflammasome in innate immune detection of bacterial flagellin and type III secretion apparatus. Immunol Rev. 2015;265(1):85–102. · DOI
  44. Xu H, Yang J, Gao W, Li L, Li P, Zhang L, et al. Innate immune sensing of bacterial modifications of Rho GTPases by the Pyrin inflammasome. Nature. 2014;513(7517):237–41. · DOI
  45. Shi J, Zhao Y, Wang K, Shi X, Wang Y, Huang H, et al. Cleavage of GSDMD by inflammatory caspases determines pyroptotic cell death. Nature. 2015;526(7575):660–5. · DOI · Paper page
  46. Taabazuing CY, Okondo MC, Bachovchin DA. Pyroptosis and Apoptosis Pathways Engage in Bidirectional Crosstalk in Monocytes and Macrophages. Cell Chem Biol. 2017;24(4):507-514 e504. · DOI
  47. Yamazaki M, Kawai M, Miyagawa K, Ohata Y, Tachikawa K, Kinoshita S, et al. Interleukin-1-induced acute bone resorption facilitates the secretion of fibroblast growth factor 23 into the circulation. J Bone Miner Metab. 2015;33(3):342–54. · DOI
  48. Li C, Qiu M, Chang L, Qi J, Zhang L, Ryffel B, et al. The osteoprotective role of USP26 in coordinating bone formation and resorption. Cell Death Differ. 2022;29(6):1123–36. · DOI
  49. Ormsby RT, Cantley M, Kogawa M, Solomon LB, Haynes DR, Findlay DM, et al. Evidence that osteocyte perilacunar remodelling contributes to polyethylene wear particle induced osteolysis. Acta Biomater. 2016;33:242–51. · DOI
  50. Hallab NJ, Jacobs JJ. Biologic effects of implant debris. Bull NYU Hosp Jt Dis. 2009;67(2):182–8.
  51. Guo Q, Wu Y, Hou Y, Liu Y, Liu T, Zhang H, et al. Cytokine Secretion and Pyroptosis of Thyroid Follicular Cells Mediated by Enhanced NLRP3, NLRP1, NLRC4, and AIM2 Inflammasomes Are Associated With Autoimmune Thyroiditis. Front Immunol. 2018;9:1197. · DOI
  52. Wang Y, Wu NN, Mu YQ, Zhang RX, Hu M, Li RD, et al. The effect of adenovirus-mediated siRNA targeting BMPR-II on UHMWPE-induced osteoclast formation. Biomaterials. 2013;34(1):150–9. · DOI
  53. Zheng J, Chang L, Bao X, Zhang X, Li C, Deng L. TRIM21 drives intervertebral disc degeneration induced by oxidative stress via mediating HIF-1alpha degradation. Biochem Biophys Res Commun. 2021;555:46–53. · DOI
  54. Chen K, Zhou Q, Kang H, Yan Y, Qian N, Li C, et al. High Mineralization Capacity of IDG-SW3 Cells in 3D Collagen Hydrogel for Bone Healing in Estrogen-Deficient Mice. Front Bioeng Biotechnol. 2020;8:864. · DOI
  55. Wu X, Zhang H, Qi W, Zhang Y, Li J, Li Z, et al. Nicotine promotes atherosclerosis via ROS-NLRP3-mediated endothelial cell pyroptosis. Cell Death Dis. 2018;9(2):171. · DOI

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Metadata

Authors
Zhao, S., Ge, C., Li, Y., Chang, L., Dan, Z., Tu, Y., Deng, L., Kang, H., & Li, C.
Affiliations
  • Tongji University (CN)
  • Shanghai Jiao Tong University (CN)
  • Nanjing Medical University (CN)
Corresponding author
  • Deng, Lianfu
  • Kang, Hui
  • Li, Changwei
Venue
Journal of Biological Engineering
Publisher
Springer Science and Business Media LLC
Published
2022-12-08
Volume
16
Issue
1
Pages
34-34
ISSN
1754-1611 (ISSN-L)
DOI
10.1186/s13036-022-00314-8
PMC
PMC9733322
OpenAlex
W4311199977
Cited by
11
References
0
Citations by year
2026: 5 · 2025: 5 · 2024: 1
FWCI
1.28
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Biological Engineering (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Science and Technology Commission of Shanghai Municipality (19140900300)
  • National Natural Science Foundation of China (81802141)
  • Shanghai Sailing Program (18YF1419200)
Topics
  • Health Sciences › Medicine › Surgery › Orthopaedic implants and arthroplasty
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
  • Health Sciences › Medicine › Surgery › Orthopedic Infections and Treatments
Keywords
deferoxamine, osteolysis, caspase-1, gasdermin D, inflammasome, IL-1β, osteoclastogenesis, bone resorption, iron chelation, MLO-Y4 cells

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