Ефекти нивоа тромбоспондина-1 (THBS1) и тол-лика рецептора 4 (TLR-4) у серуму и синовијалној течности код пацијената са остеоартритисом колена
Нивои THBS1 и TLR-4 код остеоартритиса колена
Sažetak
Objective To explore the changes in and significance of Thrombospondin-1 (THBS1) and Toll-like receptor 4 (TLR-4) levels in the serum and joint fluid of patients with knee osteoarthritis (KOA).
Methods 184 KOA patients who were admitted to our hospital between May 2022 and February 2025 were chosen to serve as the observation group, and another 64 healthy adults who underwent physical examinations at the same hospital during the same period composed the control group. Tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, THBS1, and TLR-4 levels in the two groups' serum and joint fluid were compared. The correlations between the levels of TNF-α, IL-1β, THBS1 and TLR-4 in the serum and synovial fluid of the two groups and the severity of KOA were evaluated, and the clinical value of THBS1 and TLR-4 in the diagnosis of KOA was analyzed.
Results TNF-α, IL-1β, THBS1, and TLR-4 levels in the observation group's serum and joint fluid were considerably higher than those in the control group (P<0.05). With an increase in Kellgren-Lawrence (K-L) grade, the observation group's serum and joint fluid had higher amounts of TNF-α, IL-1β, THBS1, and TLR-4. When TNF-α, IL-1β, THBS1, and TLR-4 levels were compared among K-L grades, statistically significant differences were found (P<0.05). The K-L grade of the patients was positively correlated with TNF-α, IL-1β, THBS1, and TLR-4 in the blood and joint fluid (P<0.05), and the factors of TNF-α, IL-1β, THBS1, and TLR-4 in the observation group's serum and joint fluid were positively correlated with each other (P<0.05). The sensitivity and specificity of serum THBS1 and TLR-4 for the diagnosis of KOA were 0.916 and 0.889 and 0.825 and 0.865, respectively, and the optimal cutoff values were 247.262 and 5.084 ng/mL, respectively. The sensitivity and specificity of THBS1 and TLR-4 in the joint fluid for diagnosing KOA were 0.945 and 0.932 and 0.985 and 0.916, respectively, and the optimal cutoff values were 239.745 and 4.620 ng/mL, respectively.
Conclusion THBS1 and TLR-4 in serum and synovial fluid can be used as potential markers for the clinical diagnosis and assessment of KOA conditions, both of which have high diagnostic efficacy. Moreover, the detection of serum THBS1 and TLR-4 is less invasive, has a lower cost, and is more acceptable to patients.
Reference
2.Liew JW, King LK, Mahmoudian A, Wang Q, Atkinson HF, Flynn DB, Appleton CT, Englund M, Haugen IK, Lohmander LS, Runhaar J, Neogi T, Hawker G; OARSI Early Osteoarthritis Classification Criteria Task Force. A scoping review of how early-stage knee osteoarthritis has been defined. Osteoarthritis Cartilage. 2023 Sep;31(9):1234-1241. doi: 10.1016/j.joca.2023.04.015. Epub 2023 May 22. PMID: 37225053; PMCID: PMC10528892.
3.Dong Y, Yan Y, Zhou J, Zhou Q, Wei H. Evidence on risk factors for knee osteoarthritis in middle-older aged: a systematic review and meta analysis. J Orthop Surg Res. 2023 Aug 29;18(1):634. doi: 10.1186/s13018-023-04089-6. PMID: 37641050; PMCID: PMC10464102.
4.Shanahan EM, Robinson L, Lyne S, Woodman R, Cai F, Dissanayake K, Paddick K, Cheung G, Voyvodic F. Genicular Nerve Block for Pain Management in Patients With Knee Osteoarthritis: A Randomized Placebo-Controlled Trial. Arthritis Rheumatol. 2023 Feb;75(2):201-209. doi: 10.1002/art.42384. Epub 2022 Nov 11. PMID: 36369781.
5.Hegde DD, Hadya Ananda K, Vavachan N. Effectiveness of Quadriceps Strength Training in Adults With Knee Osteoarthritis: A Systematized Review. Musculoskeletal Care. 2025 Jun;23(2):e70134. doi: 10.1002/msc.70134. PMID: 40462206.
6.Soetjahjo B, Adriansyah D, Yudistira MB, Rahman AN, Herman H, Diwan S. The Analgesic Effectiveness of Genicular Nerve-targeted Cooled and Pulsed Radiofrequency Ablation for Osteoarthritis Knee Pain: A Systematic Review and Meta-analysis. Pain Physician. 2024 Sep;27(7):357-373. PMID: 39353105.
7.Jiang Y, Tan Y, Cheng L, Wang J. Effects of three types of resistance training on knee osteoarthritis: A systematic review and network meta-analysis. PLoS One. 2024 Dec 5;19(12):e0309950. doi: 10.1371/journal.pone.0309950. PMID: 39636953; PMCID: PMC11620422.
8.Hu Z, Chen L, Zhao J, Zhang W, Jin Z, Sun Y, Li Z, Chang B, Shen P, Yang Y. Lipoxin A4 ameliorates knee osteoarthritis progression in rats by antagonizing ferroptosis through activation of the ESR2/LPAR3/Nrf2 axis in synovial fibroblast-like synoviocytes. Redox Biol. 2024 Jul;73:103143. doi: 10.1016/j.redox.2024.103143. Epub 2024 Mar 30. PMID: 38754271; PMCID: PMC11126537.
9.Castagno S, Birch M, van der Schaar M, McCaskie A. Predicting rapid progression in knee osteoarthritis: a novel and interpretable automated machine learning approach, with specific focus on young patients and early disease. Ann Rheum Dis. 2025 Jan;84(1):124-135. doi: 10.1136/ard-2024-225872. Epub 2025 Jan 2. PMID: 39874226.
10.Petrigna L, Amato A, Roggio F, Trovato B, Musumeci G. Thermal threshold for knee osteoarthritis people evaluated with infrared thermography: A scoping review. J Therm Biol. 2024 Jul;123:103932. doi: 10.1016/j.jtherbio.2024.103932. Epub 2024 Aug 3. PMID: 39111061.
11.He D, Liu X, Yang W, Guan T, Wang G. The role of mechanosensitive ion channel Piezo1 in knee osteoarthritis inflammation. Channels (Austin). 2024 Dec;18(1):2393088. doi: 10.1080/19336950.2024.2393088. Epub 2024 Aug 22. PMID: 39169878; PMCID: PMC11346567.
12.Wu L, Li X, Yan J. Commentary: Machine learning developed an intratumor heterogeneity signature for predicting prognosis and immunotherapy benefits in cholangiocarcinoma. Transl Oncol. 2024 Jul;45:101995. doi: 10.1016/j.tranon.2024.101995. Epub 2024 May 9. PMID: 38789241.
13.Pesare E, Vicenti G, Kon E, Berruto M, Caporali R, Moretti B, Randelli PS. Italian Orthopedic and Traumatology Society (SIOT) position statement on the nonsurgical management of knee osteoarthritis. J Orthop Traumatol. 2023 Sep 7;24(1):47. doi: 10.1186/s10195-023-00729-z. PMID: 37679552; PMCID: PMC10485223.
14.Fazilat-Panah D, Javadinia SA, Shabestani Monfared A, Attarian F, Babaei M, Yousefghahari B, Najafzadeh Sadati S, Ahmadi N, Fallah Tafti H. Effects of low dose rate radiotherapy on pain relief, performance score, and quality of life in patients with knee osteoarthritis; a double-blind sham-controlled randomized clinical trial. Int J Radiat Biol. 2025;101(5):541-548. doi: 10.1080/09553002.2025.2473975. Epub 2025 Mar 5. PMID: 40043233.
15.Liu Q, Liu J, Cao G, Liu Y, Huang Y, Jiang X. Ozone therapy for knee osteoarthritis: a literature visualization analysis of research hotspots and prospects. Med Gas Res. 2025 Jun 1;15(2):356-365. doi: 10.4103/mgr.MEDGASRES-D-24-00099. Epub 2024 Dec 7. PMID: 39648327; PMCID: PMC11918477.
16.Wu L, Chen X, Zeng Q, Lai Z, Fan Z, Ruan X, Li X, Yan J. NR5A2 gene affects the overall survival of LUAD patients by regulating the activity of CSCs through SNP pathway by OCLR algorithm and immune score. Heliyon. 2024 Mar 28;10(7):e28282. doi: 10.1016/j.heliyon.2024.e28282. PMID: 38601554; PMCID: PMC11004709.
17.Szilagyi IA, Waarsing JH, van Meurs JBJ, Bierma-Zeinstra SMA, Schiphof D. A systematic review of the sex differences in risk factors for knee osteoarthritis. Rheumatology (Oxford). 2023 Jun 1;62(6):2037-2047. doi: 10.1093/rheumatology/keac688. PMID: 36495186; PMCID: PMC10234207.
18.Parhar D, Dhatt R, Liu SH, Slater A, Liu L, Khan N, Badii M, Masri B, Liu DM. Advances in Interventional Radiology Technology for the Treatment of Knee Osteoarthritis. Orthop Clin North Am. 2024 Oct;55(4):435-443. doi: 10.1016/j.ocl.2024.04.005. Epub 2024 May 30. PMID: 39216948.
19.Chang AH, Almagor O, Lee JJ, Song J, Muhammad LN, Chmiel JS, Moisio KC, Sharma L. The Natural History of Knee Osteoarthritis Pain Experience and Risk Profiles. J Pain. 2023 Dec;24(12):2175-2185. doi: 10.1016/j.jpain.2023.07.002. Epub 2023 Jul 11. PMID: 37442402; PMCID: PMC10782816.
20.Panwar P, Chaurasia S, Gangrade J, Bilandi A. Early diagnosis of knee osteoarthritis severity using vision transformer. BMC Musculoskelet Disord. 2025 Sep 30;26(1):884. doi: 10.1186/s12891-025-09137-2. PMID: 41029374; PMCID: PMC12487547.
21.Tong B, Chen H, Wang C, Zeng W, Li D, Liu P, Liu M, Jin X, Shang S. Clinical prediction models for knee pain in patients with knee osteoarthritis: a systematic review. Skeletal Radiol. 2024 Jun;53(6):1045-1059. doi: 10.1007/s00256-024-04590-x. Epub 2024 Jan 24. PMID: 38265451.
22.Liu B, Xu HY, Zhang R, Han L, Li Y, Sun XF. An Update on Clinical Utility of Musculoskeletal Ultrasonography in Knee Osteoarthritis. J Ultrasound Med. 2023 Jul;42(7):1413-1422. doi: 10.1002/jum.16176. Epub 2023 Jan 30. PMID: 36715025.
23.Wu L, Li X, Qian X, Wang S, Liu J, Yan J. Lipid Nanoparticle (LNP) Delivery Carrier-Assisted Targeted Controlled Release mRNA Vaccines in Tumor Immunity. Vaccines (Basel). 2024 Feb 12;12(2):186. doi: 10.3390/vaccines12020186. PMID: 38400169; PMCID: PMC10891594.
24.Tidwell CM, DeMarco PJ. Temperature-Mediated Neural Interventions in Knee Osteoarthritis: a Review of Cryoneurolysis and Cooled Radiofrequency Ablation with Ultrasound Guidance. Curr Rheumatol Rep. 2024 Mar;26(3):89-95. doi: 10.1007/s11926-023-01127-4. Epub 2023 Dec 21. PMID: 38127092.
25.Holzbauer M, Priglinger E, Kølle ST, Prantl L, Stadler C, Winkler PW, Gotterbarm T, Duscher D. Intra-Articular Application of Autologous, Fat-Derived Orthobiologics in the Treatment of Knee Osteoarthritis: A Systematic Review. Cells. 2024 Apr 25;13(9):750. doi: 10.3390/cells13090750. PMID: 38727286; PMCID: PMC11083621.
26.Wu L, Li H, Liu Y, Fan Z, Xu J, Li N, Qian X, Lin Z, Li X, Yan J. Research progress of 3D-bioprinted functional pancreas and in vitro tumor models. International Journal of Bioprinting. 2024, 10(1), 1256. doi: 10.36922/ijb.1256.
27.Wilson TG, Baghel M, Kaur N, Datta I, Loveless I, Potla P, Mendez D, Hansen L, Baker K, Lynch TS, Moutzouros V, Davis J, Ali SA. Circulating miR-126-3p is a mechanistic biomarker for knee osteoarthritis. Nat Commun. 2025 Feb 27;16(1):2021. doi: 10.1038/s41467-025-57308-5. PMID: 40016267; PMCID: PMC11868599.
28.Dai Z, Yang T, Liu J. Contralateral knee osteoarthritis is a risk factor for ipsilateral knee osteoarthritis progressing: a case control study. BMC Musculoskelet Disord. 2024 Mar 2;25(1):190. doi: 10.1186/s12891-024-07292-6. PMID: 38431551; PMCID: PMC10908155.
29.Shetty S, Maiya GA, kg MR, Vijayan S, George BM. Effect of Core Exercises on Clinical and Functional Outcomes After Total Knee Arthroplasty in Individuals With Knee Osteoarthritis: A Systematic Review. Musculoskeletal Care. 2024 Sep;22(3):e1930. doi: 10.1002/msc.1930. PMID: 39180196.
30.Wu L, Zhong Y, Yu X, Wu D, Xu P, Lv L, Ruan X, Liu Q, Feng Y, Liu J, Li X. Selective poly adenylation predicts the efficacy of immunotherapy in patients with lung adenocarcinoma by multiple omics research. Anticancer Drugs. 2022 Oct 1;33(9):943-959. doi: 10.1097/CAD.0000000000001319. Epub 2022 Aug 9. PMID: 35946526; PMCID: PMC9481295.
31.Grenier JP, Rothmund M, Missmann M. Variation in the utilization of physiotherapy in patients with advanced knee osteoarthritis prior to total knee arthroplasty a systematic review. Musculoskeletal Care. 2023 Jun;21(2):338-354. doi: 10.1002/msc.1726. Epub 2022 Dec 20. PMID: 36539952.
32.Martel-Pelletier J, Pelletier JP. Next-Level Prediction of Structural Progression in Knee Osteoarthritis: A Perspective. Int J Mol Sci. 2025 May 15;26(10):4748. doi: 10.3390/ijms26104748. PMID: 40429891; PMCID: PMC12112129.
33.Kitagawa T, Isaji Y, Sasaki D, Onishi K, Hayashi M, Okuyama W. Effectiveness of exercise therapy in patients with knee osteoarthritis: an overview of systematic reviews. BMJ Open. 2025 Jul 16;15(7):e093163. doi: 10.1136/bmjopen-2024-093163. PMID: 40669904; PMCID: PMC12273085.
34.Prior JL, Vesentini G, Michell De Gregorio JA, Ferreira PH, Hunter DJ, Ferreira ML. Health Coaching for Low Back Pain and Hip and Knee Osteoarthritis: A Systematic Review with Meta-Analysis. Pain Med. 2023 Jan 4;24(1):32-51. doi: 10.1093/pm/pnac099. PMID: 35775931; PMCID: PMC9825146.
35.Filippiadis D, Soulez G, Cornelis FH. Genicular artery embolization for symptomatic knee osteoarthritis: New perspectives on the temporary-permanent dilemma. Diagn Interv Imaging. 2024 Apr;105(4):125-126. doi: 10.1016/j.diii.2023.12.004. Epub 2023 Dec 22. PMID: 38142181.
Sva prava zadržana (c) 2025 Yingjie Xu, Zhen Tian, Mingjin Liang, Xiaoyun Li

Ovaj rad je pod Creative Commons Autorstvo 4.0 međunarodnom licencom.
The published articles will be distributed under the Creative Commons Attribution 4.0 International License (CC BY). It is allowed to copy and redistribute the material in any medium or format, and remix, transform, and build upon it for any purpose, even commercially, as long as appropriate credit is given to the original author(s), a link to the license is provided and it is indicated if changes were made. Users are required to provide full bibliographic description of the original publication (authors, article title, journal title, volume, issue, pages), as well as its DOI code. In electronic publishing, users are also required to link the content with both the original article published in Journal of Medical Biochemistry and the licence used.
Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.
