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Mechanics and biology interact in a feed-forward manner in that imbalanced joint loading leads to tissue degeneration and vice versa. Amid numerous genetic factors, the Secretory Leukocyte Protease Inhibitor (SLPI) gene encodes a protein that plays a crucial role in inhibiting proteases, modulating inflammation, promoting tissue repair, and regulating immune responses. In the context of OA, SLPI has been identified as a key regulator in joint homeostasis. The release of SLPI in human tissues is augmented by pro-inflammatory factors. Such factors include cytokines released during infection or inflammatory processes, such as interleukins-1 and 6 (IL-1 and IL-6), and tumor necrosis factor alpha (TNF-\u03b1) released in many inflammatory rheumatic diseases. In this work, a comprehensive review of SLPI-mediated inflammation in OA, its biological functions, and its association with OA is described, providing a foundation for future investigations into its potential therapeutic use. As there is no effective strategy to treat or prevent OA in clinic, further investigation is encouraged to explore the translational possibility of SLPI for drug development.<\/jats:p>","DOI":"10.3390\/biom15070909","type":"journal-article","created":{"date-parts":[[2025,6,20]],"date-time":"2025-06-20T08:13:56Z","timestamp":1750407236000},"page":"909","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["The Role of SLPI Gene-Mediated Inflammation in Osteoarthritis"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-1721-1271","authenticated-orcid":false,"given":"Mahmuda Siddika","family":"Shefa","sequence":"first","affiliation":[{"name":"Department of Biochemistry, Institute of Medical Science, School of Medicine, Gyeongsang National University, Jinju 52727, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5093-1060","authenticated-orcid":false,"given":"Wanil","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Institute of Medical Science, School of Medicine, Gyeongsang National University, Jinju 52727, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1016\/j.bjoms.2021.06.017","article-title":"Osteoarthritis of the temporomandibular joint: A review of aetiology and pathogenesis","volume":"60","author":"Delpachitra","year":"2022","journal-title":"Br. J. Oral Maxillofac. Surg."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"29","DOI":"10.2463\/mrms.rev.2021-0052","article-title":"Review of Quantitative Knee Articular Cartilage MR Imaging","volume":"21","author":"Banjar","year":"2022","journal-title":"Magn. Reson. Med. Sci."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Ho, J., Mak, C., Sharma, V., To, K., and Khan, W. (2022). Mendelian Randomization Studies of Lifestyle-Related Risk Factors for Osteoarthritis: A PRISMA Review and Meta-Analysis. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms231911906"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"105369","DOI":"10.1016\/j.phrs.2020.105369","article-title":"Common risk factors and therapeutic targets in obstructive sleep apnea and osteoarthritis: An unexpectable link?","volume":"164","author":"Gaspar","year":"2021","journal-title":"Pharmacol. Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1861","DOI":"10.1080\/10717544.2021.1971798","article-title":"Targeted treatment for osteoarthritis: Drugs and delivery system","volume":"28","author":"Mao","year":"2021","journal-title":"Drug Deliv."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"990","DOI":"10.2106\/JBJS.22.01124","article-title":"Gene Expression in Glenoid Articular Cartilage Varies Across Acute Instability, Chronic Instability, and Osteoarthritis","volume":"105","author":"Aleem","year":"2023","journal-title":"J. Bone Jt. Surg. Am."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1089\/ten.tec.2020.0309","article-title":"Current Models for Development of Disease-Modifying Osteoarthritis Drugs","volume":"27","author":"Makarczyk","year":"2021","journal-title":"Tissue Eng. Part C Methods"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Fu, K., Si, S., Jin, X., Zhang, Y., Duong, V., Cai, Q., Li, G., Oo, W.M., Zheng, X., and Boer, C.G. (2024). Exploring antidiabetic drug targets as potential disease-modifying agents in osteoarthritis. eBioMedicine, 107.","DOI":"10.1016\/j.ebiom.2024.105285"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"903","DOI":"10.2147\/CCID.S358897","article-title":"The Role of Recombinant Secretory Leukocyte Protease Inhibitor to CD163, FGF-2, IL-1 and IL-6 Expression in Skin Wound Healing","volume":"15","author":"Munadziroh","year":"2022","journal-title":"Clin. Cosmet. Investig. Dermatol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1177\/19476035221144746","article-title":"Toward New Assessment of Knee Cartilage Degeneration","volume":"14","author":"Aubonnet","year":"2023","journal-title":"Cartilage"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Brown, R., Dougan, C., Ferris, P., Delaney, R., Houston, C.J., Rodgers, A., Downey, D.G., Mall, M.A., Connolly, B., and Small, D. (2024). SLPI deficiency alters airway protease activity and induces cell recruitment in a model of muco-obstructive lung disease. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1433642"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1084\/jem.190.4.535","article-title":"Secretory leukocyte protease inhibitor suppresses the inflammation and joint damage of bacterial cell wall-induced arthritis","volume":"190","author":"Song","year":"1999","journal-title":"J. Exp. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1016\/j.joca.2021.01.003","article-title":"Overexpression of secretory leukocyte peptidase inhibitor (SLPI) does not modulate experimental osteoarthritis but may be a biomarker for the disease","volume":"29","author":"Kim","year":"2021","journal-title":"Osteoarthr. Cartil."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/j.joca.2022.10.004","article-title":"Osteoarthritis year in review 2022: Rehabilitation","volume":"31","author":"Holden","year":"2023","journal-title":"Osteoarthr. Cartil."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Cai, X., Yuan, S., Zeng, Y., Wang, C., Yu, N., and Ding, C. (2021). New Trends in Pharmacological Treatments for Osteoarthritis. Front. Pharmacol., 12.","DOI":"10.3389\/fphar.2021.645842"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1234","DOI":"10.1016\/j.joca.2023.04.015","article-title":"A scoping review of how early-stage knee osteoarthritis has been defined","volume":"31","author":"Liew","year":"2023","journal-title":"Osteoarthr. Cartil."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e14092","DOI":"10.1111\/acel.14092","article-title":"Osteoclasts and osteoarthritis: Novel intervention targets and therapeutic potentials during aging","volume":"23","author":"Wang","year":"2024","journal-title":"Aging Cell"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e13918","DOI":"10.1111\/1440-1681.13918","article-title":"Ellagic acid improves osteoarthritis by inhibiting PGE2 production in M1 macrophages via targeting PTGS2","volume":"51","author":"Zhang","year":"2024","journal-title":"Clin. Exp. Pharmacol. Physiol."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Horv\u00e1th, E., S\u00f3lyom, \u00c1., Sz\u00e9kely, J., Nagy, E.E., and Popoviciu, H. (2023). Inflammatory and Metabolic Signaling Interfaces of the Hypertrophic and Senescent Chondrocyte Phenotypes Associated with Osteoarthritis. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms242216468"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"886","DOI":"10.1016\/j.joca.2022.03.007","article-title":"The regional turnover of cartilage collagen matrix in late-stage human knee osteoarthritis","volume":"30","author":"Agergaard","year":"2022","journal-title":"Osteoarthr. Cartil."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1016\/j.cpm.2022.02.002","article-title":"Histophysiology of Fibrocartilage","volume":"39","author":"Pirozzi","year":"2022","journal-title":"Clin. Podiatr. Med. Surg."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1016\/j.joca.2021.10.016","article-title":"The relation between the biochemical composition of knee articular cartilage and quantitative MRI: A systematic review and meta-analysis","volume":"30","author":"Emanuel","year":"2022","journal-title":"Osteoarthr. Cartil."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1148\/radiol.2021211957","article-title":"Standardization of Compositional MRI of Knee Cartilage: Why and How","volume":"301","author":"Kijowski","year":"2021","journal-title":"Radiology"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1016\/j.actbio.2022.09.002","article-title":"The intrinsic quality of proteoglycans, but not collagen fibres, degrades in osteoarthritic cartilage","volume":"153","author":"Moo","year":"2022","journal-title":"Acta Biomater."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Shiozawa, J., de Vega, S., Yoshinaga, C., Ji, X., Negishi, Y., Momoeda, M., Nakamura, T., Yoshida, H., Kaneko, H., and Ishijima, M. (2022). Expression and regulation of recently discovered hyaluronidases, HYBID and TMEM2, in chondrocytes from knee osteoarthritic cartilage. Sci. Rep., 12.","DOI":"10.1038\/s41598-022-22230-z"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Cui, J., and Zhang, J. (2022). Cartilage Oligomeric Matrix Protein, Diseases, and Therapeutic Opportunities. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23169253"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"701","DOI":"10.3724\/abbs.2023086","article-title":"The role of mechano growth factor in chondrocytes and cartilage defects: A concise review","volume":"55","author":"Liu","year":"2023","journal-title":"ABBS"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1271","DOI":"10.1128\/IAI.73.3.1271-1274.2005","article-title":"Anti-Inflammatory and Antimicrobial Roles of Secretory Leukocyte Protease Inhibitor","volume":"73","author":"Doumas","year":"2005","journal-title":"Infect. Immun."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"33389","DOI":"10.1074\/jbc.M706884200","article-title":"Secretory Leucocyte Protease Inhibitor Inhibits Interferon-\u03b3-induced Cathepsin S Expression","volume":"282","author":"Geraghty","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"3684","DOI":"10.1128\/IAI.72.6.3684-3687.2004","article-title":"Secretory Leucoprotease Inhibitor Impairs Toll-Like Receptor 2- and 4-Mediated Responses in Monocytic Cells","volume":"72","author":"Greene","year":"2004","journal-title":"Infect. Immun."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1046\/j.1365-2249.2000.01269.x","article-title":"Effects of secretory leucocyte protease inhibitor on the production of the anti-inflammatory cytokines, IL-10 and transforming growth factor-beta (TGF-beta), by lipopolysaccharide-stimulated macrophages","volume":"121","author":"Sano","year":"2000","journal-title":"Clin. Exp. Immunol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2242","DOI":"10.1001\/jama.2022.21893","article-title":"Effect of Diet and Exercise on Knee Pain in Patients With Osteoarthritis and Overweight or Obesity: A Randomized Clinical Trial","volume":"328","author":"Messier","year":"2022","journal-title":"JAMA"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1016\/j.jpain.2021.07.012","article-title":"Prevalence, Incidence, and Factors Associated With Non-Specific Chronic Low Back Pain in Community-Dwelling Older Adults Aged 60 Years and Older: A Systematic Review and Meta-Analysis","volume":"23","author":"Wong","year":"2022","journal-title":"J. Pain"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1177\/08982643231153459","article-title":"Association of Osteoarthritis and Functional Limitations With Cognitive Impairment Among Older Adults in the United States","volume":"35","author":"Rakutt","year":"2023","journal-title":"J. Aging Health"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"e225","DOI":"10.1016\/S2665-9913(23)00060-7","article-title":"The influence of sex hormones on musculoskeletal pain and osteoarthritis","volume":"5","author":"Gulati","year":"2023","journal-title":"Lancet Rheumatol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"110453","DOI":"10.1016\/j.intimp.2023.110453","article-title":"Extracellular matrix in synovium development, homeostasis and arthritis disease","volume":"121","author":"Wei","year":"2023","journal-title":"Int. Immunopharmacol."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Shi, D., Mei, Y., Hao, W., Li, J., Liu, S., and Lin, X. (2023). Biological functions and applications of LncRNAs in the regulation of the extracellular matrix in osteoarthritis. Front. Cell Dev. Biol., 11.","DOI":"10.3389\/fcell.2023.1330624"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1007\/s00223-020-00739-7","article-title":"Targeting Dysregulation of Metalloproteinase Activity in Osteoarthritis","volume":"109","author":"Yamamoto","year":"2021","journal-title":"Calcif. Tissue Int."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1038\/s41584-023-00966-w","article-title":"Matrix metalloproteinases in arthritis: Towards precision medicine","volume":"19","author":"Grillet","year":"2023","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Kulkarni, P., Harsulkar, A., M\u00e4rtson, A.-G., Suutre, S., M\u00e4rtson, A., and Koks, S. (2022). Mast Cells Differentiated in Synovial Fluid and Resident in Osteophytes Exalt the Inflammatory Pathology of Osteoarthritis. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23010541"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"898S","DOI":"10.1177\/1947603519888787","article-title":"LINC01534 Promotes the Aberrant Metabolic Dysfunction and Inflammation in IL-1\u03b2-Simulated Osteoarthritic Chondrocytes by Targeting miR-140-5p","volume":"13","author":"Wei","year":"2021","journal-title":"Cartilage"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1186\/s13018-024-04583-5","article-title":"PDK4 inhibits osteoarthritis progression by activating the PPAR pathway","volume":"19","author":"Li","year":"2024","journal-title":"J. Orthop. Surg. Res."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Elkhenany, H.A., Linardi, R.L., and Ortved, K.F. (2024). Differential modulation of inflammatory cytokines by recombinant IL-10 in IL-1\u03b2 and TNF-\u03b1\u2014stimulated equine chondrocytes and synoviocytes: Impact of washing and timing on cytokine responses. BMC Vet. Res., 20.","DOI":"10.1186\/s12917-024-04403-2"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"109982","DOI":"10.1016\/j.intimp.2023.109982","article-title":"Syringaresinol attenuates osteoarthritis via regulating the NF-\u03baB pathway","volume":"118","author":"Wang","year":"2023","journal-title":"Int. Immunopharmacol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2283","DOI":"10.1038\/s12276-024-01330-y","article-title":"FTO-mediated SMAD2 m6A modification protects cartilage against Osteoarthritis","volume":"56","author":"Zhou","year":"2024","journal-title":"Exp. Mol. Med."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Wang, L., and He, C. (2022). Nrf2-mediated anti-inflammatory polarization of macrophages as therapeutic targets for osteoarthritis. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.967193"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/j.cytogfr.2015.12.001","article-title":"Secretory leukocyte protease inhibitor (SLPI), a multifunctional protein in the host defense response","volume":"28","author":"Majewski","year":"2016","journal-title":"Cytokine Growth Factor Rev."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2866","DOI":"10.1016\/j.ajpath.2011.02.017","article-title":"Secretory Leukocyte Protease Inhibitor (SLPI) Expression and Tumor Invasion in Oral Squamous Cell Carcinoma","volume":"178","author":"Wen","year":"2011","journal-title":"Am. J. Pathol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2464","DOI":"10.1161\/ATVBAHA.111.231563","article-title":"Selective Inhibition of Matrix Metalloproteinase-13 Increases Collagen Content of Established Mouse Atherosclerosis","volume":"31","author":"Quillard","year":"2011","journal-title":"ATVB"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1002\/pro.64","article-title":"Protease inhibitors derived from elafin and SLPI and engineered to have enhanced specificity towards neutrophil serine proteases","volume":"18","author":"Zani","year":"2009","journal-title":"Protein Sci."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1000","DOI":"10.1002\/emmm.201202100","article-title":"Matrix metalloproteinase 13 modulates intestinal epithelial barrier integrity in inflammatory diseases by activating TNF","volume":"5","author":"Vandenbroucke","year":"2013","journal-title":"EMBO Mol. Med."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1016\/j.actbio.2021.02.042","article-title":"Cryptic ligand on collagen matrix unveiled by MMP13 accelerates bone tissue regeneration via MMP13\/Integrin \u03b13\/RUNX2 feedback loop","volume":"125","author":"Arai","year":"2021","journal-title":"Acta Biomater."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1007\/s00018-025-05606-y","article-title":"SLPI controls neutrophil migration abilities and impacts neutrophil skin infiltration in experimental psoriasis","volume":"82","author":"Kwiecinska","year":"2025","journal-title":"Cell Mol. Life Sci."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Migita, K., Izumi, Y., Jiuchi, Y., Kozuru, H., Kawahara, C., Nakamura, M., Nakamura, T., Agematsu, K., Masumoto, J., and Yasunami, M. (2014). Serum amyloid A induces NLRP-3-mediated IL-1\u03b2 secretion in neutrophils. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0096703"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1164\/rccm.201211-2139OC","article-title":"Serum amyloid A promotes lung neutrophilia by increasing IL-17A levels in the mucosa and \u03b3\u03b4 T cells","volume":"188","author":"Anthony","year":"2013","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"e24550","DOI":"10.1016\/j.heliyon.2024.e24550","article-title":"The secretory leukocyte protease inhibitor (SLPI) in pathophysiology of non-communicable diseases: Evidence from experimental studies to clinical applications","volume":"10","author":"Mongkolpathumrat","year":"2024","journal-title":"Heliyon"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"ra10","DOI":"10.1126\/scisignal.2005568","article-title":"Leukotriene B4-mediated sterile inflammation promotes susceptibility to sepsis in a mouse model of type 1 diabetes","volume":"8","author":"Filgueiras","year":"2015","journal-title":"Sci. Signal"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"856","DOI":"10.1136\/ard.2009.113043","article-title":"Radiographic severity of knee osteoarthritis is conditional on interleukin 1 receptor antagonist gene variations","volume":"69","author":"Attur","year":"2010","journal-title":"Ann. Rheum. Dis."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1136\/annrheumdis-2019-216055","article-title":"Interleukin 1 receptor antagonist (IL1RN) gene variants predict radiographic severity of knee osteoarthritis and risk of incident disease","volume":"79","author":"Attur","year":"2020","journal-title":"Ann. Rheum. Dis."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1908","DOI":"10.1002\/art.30360","article-title":"Increased interleukin-1\u03b2 gene expression in peripheral blood leukocytes is associated with increased pain and predicts risk for progression of symptomatic knee osteoarthritis","volume":"63","author":"Attur","year":"2011","journal-title":"Arthritis Rheum."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1437","DOI":"10.1042\/BST0391437","article-title":"SLPI and elafin: Multifunctional antiproteases of the WFDC family","volume":"39","author":"Scott","year":"2011","journal-title":"Biochem. Soc. Trans."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1016\/j.joca.2009.11.015","article-title":"Osteochondral angiogenesis and increased protease inhibitor expression in OA","volume":"18","author":"McWilliams","year":"2010","journal-title":"Osteoarthr. Cartil."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"154633","DOI":"10.1016\/j.prp.2023.154633","article-title":"Secretory leukocyte protease inhibitor (SLPI) in cancer pathophysiology: Mechanisms of action and clinical implications","volume":"248","author":"Zhang","year":"2023","journal-title":"Pathol. Res. Pract."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1067","DOI":"10.1007\/s10571-020-00799-1","article-title":"The Inhibition of Inflammatory Signaling Pathway by Secretory Leukocyte Protease Inhibitor can Improve Spinal Cord Injury","volume":"40","author":"Tang","year":"2020","journal-title":"Cell. Mol. Neurobiol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"2082","DOI":"10.1080\/15548627.2020.1822097","article-title":"Mitophagy in degenerative joint diseases","volume":"17","author":"Sun","year":"2021","journal-title":"Autophagy"},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Molnar, V., Mati\u0161i\u0107, V., Kodvanj, I., Bjelica, R., Jele\u010d, \u017d., Hudetz, D., Rod, E., \u010cukelj, F., Vrdoljak, T., and Vidovi\u0107, D. (2021). Cytokines and Chemokines Involved in Osteoarthritis Pathogenesis. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22179208"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"712","DOI":"10.1177\/00220345241242389","article-title":"Inflammation Triggers Chondrocyte Ferroptosis in TMJOA via HIF-1\u03b1\/TFRC","volume":"103","author":"Chen","year":"2024","journal-title":"J. Dent. Res."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1002\/bip.22166","article-title":"Influence of secretory leukocyte protease inhibitor-based peptides on elastase activity and their incorporation in hyaluronic acid hydrogels for chronic wound therapy","volume":"98","author":"Barros","year":"2012","journal-title":"Biopolymers"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"507315","DOI":"10.1155\/2015\/507315","article-title":"The Ability of Secretory Leukocyte Protease Inhibitor to Inhibit Apoptosis in Monocytes Is Independent of Its Antiprotease Activity","volume":"2015","author":"McGarry","year":"2015","journal-title":"J. Immunol. Res."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"592","DOI":"10.1200\/JCO.2022.40.4_suppl.592","article-title":"Secretory leukocyte proteinase inhibitor: A key player in the dialogue between the tumor and its microenvironment in pancreatic cancer patients","volume":"40","author":"Chuluyan","year":"2022","journal-title":"J. Clin. Oncol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"A5","DOI":"10.1136\/annrheumdis-2013-205124.12","article-title":"A1.12 Endogenous SLPI released by rheumatoid synovial fibroblasts control BAFF-dependent-B cell activation in vitro and in the CIA and RA\/SCID-arthritis models","volume":"73","author":"Kam","year":"2014","journal-title":"Ann. Rheum. Dis."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1165\/ajrcmb.23.3.3942","article-title":"Secretory leukoprotease inhibitor augments hepatocyte growth factor production in human lung fibroblasts","volume":"23","author":"Kikuchi","year":"2000","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1016\/S0092-8674(00)81880-2","article-title":"Secretory leukocyte protease inhibitor: A macrophage product induced by and antagonistic to bacterial lipopolysaccharide","volume":"88","author":"Jin","year":"1997","journal-title":"Cell"},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"M\u00fcller, A.M., Jun, E., Conlon, H., and Sadiq, S.A. (2012). Inhibition of SLPI ameliorates disease activity in experimental autoimmune encephalomyelitis. BMC Neurosci., 13.","DOI":"10.1186\/1471-2202-13-30"},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Niu, W., Zhang, T., and Ma, L. (2023). Correlation analysis between immune-related genes and cell infiltration revealed prostate cancer immunotherapy biomarkers linked to T cells gamma delta. Sci. Rep., 13.","DOI":"10.1038\/s41598-023-28475-6"},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Leelasukseree, R., Chouyratchakarn, W., Phutiyothin, C., Pikwong, F., Srisopar, O., Baipaywad, P., Udomsom, S., Mongkolpathumrat, P., Supanchart, C., and Kumphune, S. (2023). Recombinant human secretory leukocyte protease inhibitor (rhSLPI) coated titanium enhanced human osteoblast adhesion and differentiation. Sci. Rep., 13.","DOI":"10.1038\/s41598-023-50565-8"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1241","DOI":"10.3892\/mmr.2016.5381","article-title":"Secretory leukocyte protease inhibitor promotes differentiation and mineralization of MC3T3-E1 preosteoblasts on a titanium surface","volume":"14","author":"Choi","year":"2016","journal-title":"Mol. Med. Rep."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1038\/s41368-022-00193-1","article-title":"Targeted inhibition of osteoclastogenesis reveals the pathogenesis and therapeutics of bone loss under sympathetic neurostress","volume":"14","author":"Sui","year":"2022","journal-title":"Int. J. Oral. Sci."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"2136","DOI":"10.1038\/s41467-021-22402-x","article-title":"SLPI is a critical mediator that controls PTH-induced bone formation","volume":"12","author":"Morimoto","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1080\/08923973.2024.2329621","article-title":"Isorhamnetin ameliorates cisplatin-induced acute kidney injury in mice by activating SLPI-mediated anti-inflammatory effect in macrophage","volume":"46","author":"Jian","year":"2024","journal-title":"Immunopharmacol. Immunotoxicol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"108292","DOI":"10.18632\/oncotarget.22660","article-title":"Secretory leukocyte protease inhibitor (SLPI) as a potential target for inhibiting metastasis of triple-negative breast cancers","volume":"8","author":"Kozin","year":"2017","journal-title":"Oncotarget"},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Ozaka, S., Sonoda, A., Kudo, Y., Ito, K., Kamiyama, N., Sachi, N., Chalalai, T., Kagoshima, Y., Soga, Y., and Ekronarongchai, S. (2024). Daikenchuto, a Japanese herbal medicine, ameliorates experimental colitis in a murine model by inducing secretory leukocyte protease inhibitor and modulating the gut microbiota. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1457562"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"e13132","DOI":"10.1111\/cpr.13132","article-title":"Reduced ELANE and SLPI expression compromises dental pulp cell activity","volume":"54","author":"Sriwattanapong","year":"2021","journal-title":"Cell Prolif."},{"key":"ref_84","doi-asserted-by":"crossref","unstructured":"Osbourn, M., Rodgers, A.M., Dubois, A.V., Small, D.M., Humphries, F., Delagic, N., Moynagh, P.N., Weldon, S., Taggart, C.C., and Ingram, R.J. (2022). Secretory Leucoprotease Inhibitor (SLPI) Promotes Survival during Acute Pseudomonas aeruginosa Infection by Suppression of Inflammation Rather Than Microbial Killing. Biomolecules, 12.","DOI":"10.20944\/preprints202210.0264.v1"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.bbrc.2005.03.138","article-title":"5-Azacytidine suppresses RNA polymerase II recruitment to the SLPI gene","volume":"331","author":"Wada","year":"2005","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1016\/j.jobcr.2022.04.001","article-title":"The effect of secretory leukocyte protease inhibitor amnion membrane on incisional wound healing","volume":"12","author":"Munadziroh","year":"2022","journal-title":"J. Oral Biol. Craniofacial Res."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1097\/BOR.0000000000000853","article-title":"Insights into the molecular landscape of osteoarthritis in human tissues","volume":"34","author":"Katsoula","year":"2022","journal-title":"Curr. Opin. Rheumatol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1038\/labinvest.2016.40","article-title":"Secretory leukocyte protease inhibitor gene deletion alters bleomycin-induced lung injury, but not development of pulmonary fibrosis","volume":"96","author":"Habgood","year":"2016","journal-title":"Lab. Invest."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1097\/00042737-200603000-00008","article-title":"Secretory leukocyte protease inhibitor expression in various types of gastritis: A specific role of Helicobacter pylori infection","volume":"18","author":"Hritz","year":"2006","journal-title":"Eur. J. Gastroenterol. Hepatol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1832761","DOI":"10.1080\/2162402X.2020.1832761","article-title":"Expression of the immune modulator secretory leukocyte protease inhibitor (SLPI) in colorectal cancer liver metastases and matched primary tumors is associated with a poorer prognosis","volume":"9","author":"Nugteren","year":"2020","journal-title":"Oncoimmunology"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"3781","DOI":"10.4049\/jimmunol.174.6.3781","article-title":"Antigen-specific B cells are required as APCs and autoantibody-producing cells for induction of severe autoimmune arthritis","volume":"174","author":"Shlomchik","year":"2005","journal-title":"J. Immunol."},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Reeves, E.P., Banville, N., Ryan, D.M., O\u2019Reilly, N., Bergin, D.A., Pohl, K., Molloy, K., McElvaney, O.J., Alsaleh, K., and Aljorfi, A. (2013). Intracellular secretory leukoprotease inhibitor modulates inositol 1,4,5-triphosphate generation and exerts an anti-inflammatory effect on neutrophils of individuals with cystic fibrosis and chronic obstructive pulmonary disease. Biomed. Res. Int., 2013.","DOI":"10.1155\/2013\/560141"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1276","DOI":"10.1097\/00003246-200005000-00003","article-title":"Secretory leukocyte protease inhibitor, an inhibitor of neutrophil activation, is elevated in serum in human sepsis and experimental endotoxemia","volume":"28","author":"Grobmyer","year":"2000","journal-title":"Crit. Care Med."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1111\/gtc.12888","article-title":"Protease inhibitory activity of secretory leukocyte protease inhibitor ameliorates murine experimental colitis by protecting the intestinal epithelial barrier","volume":"26","author":"Ozaka","year":"2021","journal-title":"Genes. Cells"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"1266","DOI":"10.1111\/jdv.18065","article-title":"Secretory leukocyte protease inhibitor regulates nerve reflex-mediated skin barrier function in psoriasis","volume":"36","author":"Kwiecinska","year":"2022","journal-title":"J. Eur. Acad. Dermatol. Venereol."},{"key":"ref_96","doi-asserted-by":"crossref","unstructured":"Afacan, B., \u00d6zt\u00fcrk, V.\u00d6., Emingil, G., K\u00f6se, T., Mitsakakis, K., and Bostanci, N. (2022). Salivary secretory leukocyte protease inhibitor levels in patients with stage 3 grade C periodontitis: A comparative cross-sectional study. Sci. Rep., 12.","DOI":"10.1038\/s41598-022-24295-2"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"726","DOI":"10.1124\/pr.110.002733","article-title":"Neutrophil elastase, proteinase 3, and cathepsin G as therapeutic targets in human diseases","volume":"62","author":"Korkmaz","year":"2010","journal-title":"Pharmacol. Rev."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"100715","DOI":"10.1016\/j.bonr.2020.100715","article-title":"Concerted actions by MMPs, ADAMTS and serine proteases during remodeling of the cartilage callus into bone during osseointegration of hip implants","volume":"13","author":"Cassuto","year":"2020","journal-title":"Bone Rep."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"894","DOI":"10.1172\/JCI119254","article-title":"Secretory leukocyte protease inhibitor suppresses the production of monocyte prostaglandin H synthase-2, prostaglandin E2, and matrix metalloproteinases","volume":"99","author":"Zhang","year":"1997","journal-title":"J. Clin. Invest."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"156471","DOI":"10.1016\/j.phymed.2025.156471","article-title":"Guizhi Shaoyao Zhimu Decoction alleviates rheumatoid arthritis by inhibiting inflammation by targeting SLPI","volume":"139","author":"Pan","year":"2025","journal-title":"Phytomedicine"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"1147","DOI":"10.1038\/80489","article-title":"Secretory leukocyte protease inhibitor mediates non-redundant functions necessary for normal wound healing","volume":"6","author":"Ashcroft","year":"2000","journal-title":"Nat. Med."}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/15\/7\/909\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:55:43Z","timestamp":1760032543000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/15\/7\/909"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,20]]},"references-count":101,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2025,7]]}},"alternative-id":["biom15070909"],"URL":"https:\/\/doi.org\/10.3390\/biom15070909","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,20]]}}}