Expression and significance of pyroptosis associated protein in peripheral tissues with tantalum cage loosening

doi:10.12307/2023.414

Abstract

Abstract: BACKGROUND: The mechanism of how the fusion cage affects its surrounding cells and eventually leads to osteolysis with aseptic loosening after implantation of the tantalum (Ta) fusion device into the intervertebral space remains to be elucidated.
OBJECTIVE: To explore the effect of pyroptosis in tantalum (Ta) induced intervertebral osteolysis.
METHODS: Patients admitted to the Department of Orthopedics, Jiangxi Provincial People’s Hospital from January 2015 to December 2021 were selected in this study. The observation group (n=19) contained the cases of lumbar fusion tantalum cage loosening and revision. The control group (n=11) consisted of autologous bone graft lumbar fusion, internal fixation removal after fusion of other material cages, and degeneration of adjacent segments implanted with tantalum cages requiring extended fixation of the fusion segment. During the operation, the limiting membrane tissue around the cage and around the fusion segment of the two groups was collected for scanning electron microscopy, immunofluorescence staining and qRT-PCR detection.
RESULTS AND CONCLUSION: (1) Electron microscopy showed that a large amount of fibrous tissue proliferation was observed around the tantalum (Ta) fusion vessel and within the boundary membrane tissue of the fused segment in the observation group. Meanwhile, irregular particles on tantalum shedding could be observed partially, but fibrous tissue proliferation was not obvious in the control group, and no irregular particles were found. (2) Hematoxylin and eosin staining showed that a large amount of fibrous tissue proliferation with indistinct osteoblasts was observed in the boundary membrane tissue around the fusions and in the fused segments, and osteoblasts were not obvious in the observation group. Fibrous tissue proliferation was not obvious in the limiting membrane tissue of the control group, and osteoblasts were seen distributed around the bone tissue. (3) Immunofluorescence examination showed that the expression of pyroptosis-related proteins GSDMD, NLRP3 and Caspase 1 in the limiting membrane tissue in the observation group was higher than that in the control group (P < 0.05). (4) qRT-PCR assay showed that mRNA expression levels of GSDMD, Caspase 1 and NLRP3 in the observation group were higher than those in the control group (P < 0.05). (5) These results showed that the expression of pyroptosis related proteins (GSDMD, NLRP3, and Caspase 1) was remarkably increased in tantalum (Ta) fusion loosening cases, indicating that pyroptosis was involved in the pathophysiology of tantalum (Ta) induced intervertebral osteolysis.

Key words: tantalum (Ta), fusion cage, pyroptosis, osteolysis, bone tissue engineering, spinal fusion, limiting membrane tissue

CLC Number:

Long Zhisheng, Fu Liuxiang, Gong Feipeng, Wen Jiabin, Deng Ying, Min Huan, Deng Zhuan, Chen Gang. Expression and significance of pyroptosis associated protein in peripheral tissues with tantalum cage loosening[J]. Chinese Journal of Tissue Engineering Research, 2023, 27(25): 4057-4062.

Figures/Tables 5

References

[1] KIENLE A, GRAF N, WILKE HJ. Does impaction of titanium-coated interbody fusion cages into the disc space cause wear debris or delamination? Spine J. 2016;16(2):235-242.
[2] QIAN H, LEI T, QIAN H, et al. Additively manufactured Tantalum implants for repairing bone defects : a systematic review. Tissue Eng Part B Rev. 2021;27(2):166-180.
[3] ZHU W, QIU J, YANG J, et al. Effect of titanium ions on the Hippo / YAP signaling pathway in regulating biological behaviors of MC3T3-E1 osteoblasts. J Appl Toxicol. 2018;38(6):824-833.
[4] 石晓岫,毛世龙,刘洋,等.钽与钛(合金)骨科材料的差异比较：理化指标及抗菌和成骨能力[J].中国组织工程研究,2021,25(4): 593-599.
[5] 马志杰,李京育,曹放,等.多孔碳化硅涂覆生物活性钽新型生物医用材料的影响因素及生物学性能[J].中国组织工程研究,2021, 25(4):558-563.
[6] HUANG G, PAN ST, QIU JX. The clinical application of porous tantalum and its new development for bone tissue engineering. Materials (Basel). 2021;14(10):2647.
[7] ZHANG L, HADDOUTI E M, WELLE K, et al. Local Cellular Responses to Metallic and Ceramic Nanoparticles from Orthopedic Joint Arthroplasty Implants. Int J Nanomedicine. 2020;15:6705-6720.
[8] PATEL MS, MCCORMICK JR, GHASEM A, et al. Tantalum: The next biomaterial in spine surgery? J Spine Surg. 2020;6(1):72-86.
[9] LÖFGREN H, ENGQUIST M, HOFFMANN P, et al. Clinical and radiological evaluation of Trabecular Metal and the Smith-Robinson technique in anterior cervical fusion for degenerative disease: A prospective, randomized, controlled study with 2-year follow-up. Eur Spine J. 2010; 19(3):464-473.
[10] KASLIWAL MK, BASKIN DS, TRAYNELIS VC. Failure of Porous Tantalum Cervical Interbody Fusion Devices. J Spinal Disord Tech. 2013;26(5): 239-245.
[11] ZHANG L, HADDOUTI EM, WELLE K, et al. Local cellular responses to metallic and ceramic nanoparticles from orthopedic joint arthroplasty implants. Int J Nanomedicine. 2020;15:6705-6720.
[12] ZHU Y, GU Y, QIAO S, et al. Bacterial and mammalian cells adhesion to tantalum-decorated micro-/nano-structured titanium. J Biomed Mater Res A. 2017;105(3):871-878.
[13] BONUTTI PM, PIVEC R, ISSA K, et al. Delamination of tantalum porous coating from a TKA due to regional dissemination of debris. Orthopedics. 2013;36(8):600-604.
[14] HALLAB NJ, SAMELKO L, HAMMOND D. The Inflammatory Effects of Breast Implant Particulate Shedding: Comparison with Orthopedic Implants. Aesthetic Surg J. 2019;39:S36-S48.
[15] HALLAB NJ. A review of the biologic effects of spine implant debris: Fact from fiction. SAS J. 2009;3(4):143-160.
[16] WANG JC, YU WD, SANDHU HS, et al. Metal debris from titanium spinal implants. Spine. 1999;24(9):899-903.
[17] DEVANT P, SHARPE AH, THIAGARAJAH JR, et al. Article Control of gasdermin D oligomerization and pyroptosis by the Ragulator-Rag-mTORC1 pathway Article Control of gasdermin D oligomerization and pyroptosis by the Ragulator-Rag-mTORC1 pathway. Cell. 2021:1-17.
[18] LIU X, XIA S, ZHANG Z, et al. Channelling inflammation : gasdermins. Nat Rev Drug Discov. 2021;20(5):384-405.
[19] LIU Y, CHEN Q, ZHU Y, et al. Non-coding RNAs in necroptosis, pyroptosis and ferroptosis in cancer metastasis. Cell Death Discov. 2021;7(1:210.
[20] CHEN C, JIANG Z, JIANG Q, et al. Caspase-3 and gasdermin E detection in peri-implantitis. Biochim Biophys Acta Mol Basis Dis. 2021;1867(11): 166217.
[21] JUAN CX, MAO Y, CAO Q, et al. Exosome-mediated pyroptosis of miR-93-TXNIP-NLRP3 leads to functional difference between M1 and M2 macrophages in sepsis induced acute kidney injury. J Cell Mol Med. 2021;25(10):4786-4799.
[22] FAN C, ZHAO X, GUO X, et al. P2X4 promotes interleukin‑1β production in osteoarthritis via NLRP1. Mol Med Rep. 2014;9(1):340-344.
[23] ZHANG L, XING R, HUANG Z, et al. Inhibition of Synovial Macrophage Pyroptosis Alleviates Synovitis and Fibrosis in Knee Osteoarthritis. Mediators Inflamm. 2019;2019:2165918.
[24] TAO Z, WANG J, WEN K, et al. Pyroptosis in Osteoblasts: A Novel Hypothesis Underlying the Pathogenesis of Osteoporosis. Front Endocrinol (Lausanne). 2021;11:1-11.
[25] PIERRE CA, CHAN M, IWAKURA Y, et al. Periprostheticosteolysis: characterizing the innate immune response to titanium wear-particles. J Orthop Res. 2010;28(11):1418-1424.
[26] BURTON L, PAGET D, BINDER NB, et al. Orthopedic wear debris mediated inflammatory osteolysis is mediated in part by NALP3 inflammasome activation. J Orthop Res. 2013;31(1):73-80.
[27] MA QL, FANG L, JIANG N, et al. Bone mesenchymal stem cell secretion of RANKL/OPG/M-CSF in response to macrophage-mediated inflammatory response influences osteogenesis on nanostructured Ti surfaces. Biomaterials. 2018;154:234-247.
[28] TSUKASAKI M, TAKAYANAGI H. Osteoimmunology: evolving concepts in bone–immune interactions in health and disease. Nat Rev Immunol. 2019;19(10):626-642.
[29] MINODA Y, KOBAYASHI A, IKEBUCHI M, et al. Periprosthetic Loss of Bone Mineral Density After Cementless Porous Tantalum and Cemented Total Knee Arthroplasties: A Mean of 11-Year Concise Follow-Up of a Previous Report. J Arthroplasty. 2020;35(11):3156-3160.