Correlation analysis of PGC-1β, HIF-1α and RETN with the degree of joint destruction in gouty arthritis

PGC-1β, HIF-1α and RETN in gouty arthritis

  • Jian Bian Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing Jiangbei Hospital.
  • Jianguo Zhang The First Affiliated Hospital of Zhengzhou University
  • Bo Zhang The First Affiliated Hospital of Zhengzhou University
  • Hongfei Shi Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University
Keywords: PGC-1β, HIF-1α, RETN, Joint destruction, Gouty arthritis, Correlation analysis

Abstract


Objective: To investigate the expression levels of resistin (RETN), hypoxia-inducible factor-1 α (HIF-1α), and peroxisome proliferator-activated receptor γ coactivator-1β (PGC-1β). in gouty arthritis (GA) patients and to analyze their correlations with the degree of joint destruction.

Methods: The GA group consisted of 134 GA patients who were admitted to the hospital between January 2023 and October 2024, while the control group consisted of 134 healthy patients who were examined physically in the hospital over the same time period. Serum PGC-1β, HIF-1α, and RETN expression levels were compared. The expression levels of PGC-1β, HIF-1α and RETN in the serum and synovial fluid of patients with different clinical characteristics in the GA group were compared. The degree of joint destruction was divided into 78 cases in the severe GA subgroup and 56 cases in the mild GA subgroup according to the VAS score of the chief complaint pain scale. Compared with PGC-1β, HIF-1α, RETN, and bone destruction factors [β-crosslinking degradation products (β-CTX), tartrate-resistant acid phosphatase-5b (TRACP5b), and nuclear factor κB receptor activator ligand (RANKL)], and inflammatory factors with different degrees of joint destruction, the expression levels of -1β (IL-1β) were analyzed, and the correlations between PGC-1β, HIF-1α, and RETN in serum and synovial fluid and the degree of joint destruction, bone destruction factors, and inflammatory factors were analyzed.

Results: The expression level of serum PGC-1β in the GA group was lower than that in the control group, while the expression levels of serum HIF-1α and RETN were greater than those in the control group (P<0.05). The expression levels of PGC-1β in the serum of GA patients at different clinical stages, affected joints, disease courses and annual attack frequencies. The expression levels of β-CTX and TRACP5b in the serum of GA patients at different clinical stages, affected joints, disease courses and annual attack frequencies, and in the severe GA subgroup were greater than those in the mild GA subgroup (P<0.05), and RANKL expression was lower than in the mild GA subgroup (P<0.05). The serum and synovial fluid levels of PGC-1β, β-CTX, TRACP5b, TNF-α, and IL-1β were negatively correlated with the degree of joint destruction and positively correlated with the level of RANKL. HIF-1α and RETN had a negative correlation with RANKL and a positive correlation with the degree of joint degradation, β-CTX, TRACP5b, TNF-α, and IL-1β.

Conclusion: PGC-1β, HIF-1α and RETN are abnormally expressed in patients with GA and are closely related to the degree of joint destruction, bone destruction factors and inflammatory factors. They are expected to become reliable indicators for evaluating the occurrence and progression of GA.

References

1.Cheng JJ, Ma XD, Ai GX, Yu QX, Chen XY, Yan F, Li YC, Xie JH, Su ZR, Xie QF. Palmatine Protects Against MSU-Induced Gouty Arthritis via Regulating the NF-κB/NLRP3 and Nrf2 Pathways. Drug Des Devel Ther. 2022 Jul 2;16:2119-2132. doi: 10.2147/DDDT.S356307. PMID: 35812134; PMCID: PMC9259749.
2.Yao TK, Lee RP, Wu WT, Chen IH, Yu TC, Yeh KT. Advances in Gouty Arthritis Management: Integration of Established Therapies, Emerging Treatments, and Lifestyle Interventions. Int J Mol Sci. 2024 Oct 9;25(19):10853. doi: 10.3390/ijms251910853. PMID: 39409183; PMCID: PMC11477016.
3.Yin C, Liu B, Dong Z, Shi S, Peng C, Pan Y, Bi X, Nie H, Zhang Y, Tai Y, Hu Q, Wang X, Shao X, An H, Fang J, Wang C, Liu B. CXCL5 activates CXCR2 in nociceptive sensory neurons to drive joint pain and inflammation in experimental gouty arthritis. Nat Commun. 2024 Apr 16;15(1):3263. doi: 10.1038/s41467-024-47640-7. PMID: 38627393; PMCID: PMC11021482.
4.Deng P, Wang S, Sun X, Qi Y, Ma Z, Pan X, Liang H, Wu J, Chen Z. Global Trends in Research of Gouty Arthritis Over Past Decade: A Bibliometric Analysis. Front Immunol. 2022 Jun 10;13:910400. doi: 10.3389/fimmu.2022.910400. PMID: 35757713; PMCID: PMC9229989.
5.Xu J, Wu M, Yang J, Zhao D, He D, Liu Y, Yan X, Liu Y, Pu D, Tan Q, Zhang L, Zhang J. Multimodal smart systems reprogramme macrophages and remove urate to treat gouty arthritis. Nat Nanotechnol. 2024 Oct;19(10):1544-1557. doi: 10.1038/s41565-024-01715-0. Epub 2024 Jul 17. PMID: 39020102.
6.Yin C, Lyu Q, Dong Z, Liu B, Zhang K, Liu Z, Yu Q, Li P, Wei Z, Tai Y, Wang C, Fang J, Liu W, Liu B. Well-defined alginate oligosaccharides ameliorate joint pain and inflammation in a mouse model of gouty arthritis. Theranostics. 2024 May 19;14(8):3082-3103. doi: 10.7150/thno.95611. PMID: 38855180; PMCID: PMC11155397.
7.Xu H, Zhang B, Chen Y, Zeng F, Wang W, Chen Z, Cao L, Shi J, Chen J, Zhu X, Xue Y, He R, Ji M, Hua Y. Type II collagen facilitates gouty arthritis by regulating MSU crystallization and inflammatory cell recruitment. Ann Rheum Dis. 2023 Mar;82(3):416-427. doi: 10.1136/ard-2022-222764. Epub 2022 Sep 15. PMID: 36109143.
8.Liu P, Xu Y, Ye J, Tan J, Hou J, Wang Y, Li J, Cui W, Wang S, Zhao Q. Qingre Huazhuo Jiangsuan Decoction promotes autophagy by inhibiting PI3K/AKT/mTOR signaling pathway to relieve acute gouty arthritis. J Ethnopharmacol. 2023 Feb 10;302(Pt A):115875. doi: 10.1016/j.jep.2022.115875. Epub 2022 Oct 31. PMID: 36328206.
9.Zhu R, Niu Y, Zhou W, Wang S, Mao J, Guo Y, Lei Y, Xiong X, Li Y, Guo L. Effect of nanoparticles on gouty arthritis: a systematic review and meta-analysis. BMC Musculoskelet Disord. 2023 Feb 14;24(1):124. doi: 10.1186/s12891-023-06186-3. PMID: 36788552; PMCID: PMC9926759.
10.Luo Z, Yang F, Hong S, Wang J, Chen B, Li L, Yang J, Yao Y, Yang C, Hu Y, Wang S, Xu T, Wu J. Role of microRNA alternation in the pathogenesis of gouty arthritis. Front Endocrinol (Lausanne). 2022 Aug 11;13:967769. doi: 10.3389/fendo.2022.967769. PMID: 36034424; PMCID: PMC9402903.
11.Zhao X, Li M, Lu Y, Wang M, Xiao J, Xie Q, He X, Shuai S. Sirt1 inhibits macrophage polarization and inflammation in gouty arthritis by inhibiting the MAPK/NF-κB/AP-1 pathway and activating the Nrf2/HO-1 pathway. Inflamm Res. 2024 Jul;73(7):1173-1184. doi: 10.1007/s00011-024-01890-9. Epub 2024 May 13. PMID: 38739197; PMCID: PMC11214610.
12.Wu L, Zheng Y, Liu J, Luo R, Wu D, Xu P, Wu D, Li X. Comprehensive evaluation of the efficacy and safety of LPV/r drugs in the treatment of SARS and MERS to provide potential treatment options for COVID-19. Aging (Albany NY). 2021 Apr 20;13(8):10833-10852. doi: 10.18632/aging.202860. Epub 2021 Apr 20. PMID: 33879634; PMCID: PMC8109137.
13.Abdelnabi M, Leelaviwat N, Liao ED, Motamedi S, Pangkanon W, Nugent K. Daptomycin-induced rhabdomyolysis complicated with acute gouty arthritis. Am J Med Sci. 2023 May;365(5):450-456. doi: 10.1016/j.amjms.2023.01.005. Epub 2023 Jan 22. PMID: 36693494.
14.Bian M, Zhu C, Nie A, Zhou Z. Guizhi Shaoyao Zhimu Decoction ameliorates gouty arthritis in rats by altering gut microbiota and improving metabolic profile. Phytomedicine. 2024 Aug;131:155800. doi: 10.1016/j.phymed.2024.155800. Epub 2024 Jun 3. PMID: 38851098.
15.Li C, Huang Y, Wu C, Qiu Y, Zhang L, Xu J, Zheng J, Zhang X, Li F, Xia D. Astilbin inhibited neutrophil extracellular traps in gouty arthritis through suppression of purinergic P2Y6 receptor. Phytomedicine. 2024 Jul 25;130:155754. doi: 10.1016/j.phymed.2024.155754. Epub 2024 May 17. PMID: 38820662.
16.Wu L, Zhong Y, Wu D, Xu P, Ruan X, Yan J, Liu J, Li X. Immunomodulatory Factor TIM3 of Cytolytic Active Genes Affected the Survival and Prognosis of Lung Adenocarcinoma Patients by Multi-Omics Analysis. Biomedicines. 2022 Sep 10;10(9):2248. doi: 10.3390/biomedicines10092248. PMID: 36140350; PMCID: PMC9496572.
17.Ni Z, Xiao Q, Xia Z, Kuang K, Yin B, Peng D. Electroacupuncture for acute gouty arthritis: a systematic review and meta-analysis of randomized controlled trials. Front Immunol. 2024 Jan 4;14:1295154. doi: 10.3389/fimmu.2023.1295154. PMID: 38239361; PMCID: PMC10794621.
18.Fu W, Ge M, Li J. Phospholipase A2 regulates autophagy in gouty arthritis: proteomic and metabolomic studies. J Transl Med. 2023 Apr 17;21(1):261. doi: 10.1186/s12967-023-04114-6. PMID: 37069596; PMCID: PMC10108447.
19.Lee KG, Hong BK, Lee S, Lee N, Kim SW, Kim D, Kim WU. Nuclear receptor coactivator 6 is a critical regulator of NLRP3 inflammasome activation and gouty arthritis. Cell Mol Immunol. 2024 Mar;21(3):227-244. doi: 10.1038/s41423-023-01121-x. Epub 2024 Jan 10. PMID: 38195836; PMCID: PMC10902316.
20.Wu L, Liu Q, Ruan X, Luan X, Zhong Y, Liu J, Yan J, Li X. Multiple Omics Analysis of the Role of RBM10 Gene Instability in Immune Regulation and Drug Sensitivity in Patients with Lung Adenocarcinoma (LUAD). Biomedicines. 2023 Jun 29;11(7):1861. doi: 10.3390/biomedicines11071861. PMID: 37509501; PMCID: PMC10377220.
21.Li N, Chen S, Deng W, Gong Z, Guo Y, Zeng S, Xu Q. Kaempferol Attenuates Gouty Arthritis by Regulating the Balance of Th17/Treg Cells and Secretion of IL-17. Inflammation. 2023 Oct;46(5):1901-1916. doi: 10.1007/s10753-023-01849-8. Epub 2023 Jun 14. PMID: 37311931.
22.Ni X, Wang Q, Ning Y, Liu J, Su Q, Lv S, Feng Y, Yang S, Yuan R, Gao H. Anemoside B4 targets NEK7 to inhibit NLRP3 inflammasome activation and alleviate MSU-induced acute gouty arthritis by modulating the NF-κB signaling pathway. Phytomedicine. 2025 Mar;138:156407. doi: 10.1016/j.phymed.2025.156407. Epub 2025 Jan 17. Erratum in: Phytomedicine. 2025 Jul;142:156819. doi: 10.1016/j.phymed.2025.156819. PMID: 39939033.
23.Wu L, Zheng Y, Ruan X, Wu D, Xu P, Liu J, Wu D, Li X. Long-chain noncoding ribonucleic acids affect the survival and prognosis of patients with esophageal adenocarcinoma through the autophagy pathway: construction of a prognostic model. Anticancer Drugs. 2022 Jan 1;33(1):e590-e603. doi: 10.1097/CAD.0000000000001189. PMID: 34338240; PMCID: PMC8670349.
24.Zhang S, Li D, Fan M, Yuan J, Xie C, Yuan H, Xie H, Gao H. Mechanism of Reactive Oxygen Species-Guided Immune Responses in Gouty Arthritis and Potential Therapeutic Targets. Biomolecules. 2024 Aug 9;14(8):978. doi: 10.3390/biom14080978. PMID: 39199366; PMCID: PMC11353092.
25.Medina JP, Bermejo-Álvarez I, Pérez-Baos S, Yáñez R, Fernández-García M, García-Olmo D, Mediero A, Herrero-Beaumont G, Largo R. MSC therapy ameliorates experimental gouty arthritis hinting an early COX-2 induction. Front Immunol. 2023 Jul 18;14:1193179. doi: 10.3389/fimmu.2023.1193179. Erratum in: Front Immunol. 2023 Dec 06;14:1345777. doi: 10.3389/fimmu.2023.1345777. PMID: 37533852; PMCID: PMC10391650.
26.Nutmakul T. A review on benefits of quercetin in hyperuricemia and gouty arthritis. Saudi Pharm J. 2022 Jul;30(7):918-926. doi: 10.1016/j.jsps.2022.04.013. Epub 2022 Apr 30. PMID: 35903522; PMCID: PMC9315272.
27.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.
28.Li C, Wu C, Li F, Xu W, Zhang X, Huang Y, Xia D. Targeting Neutrophil Extracellular Traps in Gouty Arthritis: Insights into Pathogenesis and Therapeutic Potential. J Inflamm Res. 2024 Mar 19;17:1735-1763. doi: 10.2147/JIR.S460333. PMID: 38523684; PMCID: PMC10960513.
29.Chen Y, Liu J, Li Y, Cong C, Hu Y, Zhang X, Han Q. The Independent Value of Neutrophil to Lymphocyte Ratio in Gouty Arthritis: A Narrative Review. J Inflamm Res. 2023 Oct 16;16:4593-4601. doi: 10.2147/JIR.S430831. PMID: 37868831; PMCID: PMC10588658.
30.Chen Z, Wang W, Hua Y. Metabolic Regulation of Immune Response and Tissue Remodeling in Gouty Arthritis (Review). Crit Rev Eukaryot Gene Expr. 2023;33(5):1-16. doi: 10.1615/CritRevEukaryotGeneExpr.2022046409. PMID: 37199310.
31.Wu C, Chen S, Liu Y, Kong B, Yan W, Jiang T, Tian H, Liu Z, Shi Q, Wang Y, Liang Q, Xi X, Xu H. Cynarin suppresses gouty arthritis induced by monosodium urate crystals. Bioengineered. 2022 May;13(5):11782-11793. doi: 10.1080/21655979.2022.2072055. PMID: 35546047; PMCID: PMC9275982.
32.Du Y, Zhang Y, Jiang Z, Xu L, Ru J, Wei S, Chen W, Dong R, Zhang S, Jia T. Triptolide alleviates acute gouty arthritis caused by monosodium urate crystals by modulating macrophage polarization and neutrophil activity. Immunol Lett. 2024 Oct;269:106907. doi: 10.1016/j.imlet.2024.106907. Epub 2024 Aug 8. PMID: 39122094.
33.Yang DH, Chen HC, Wei JC. Early urate-lowering therapy in gouty arthritis with acute flares: a double-blind placebo controlled clinical trial. Eur J Med Res. 2023 Jan 6;28(1):10. doi: 10.1186/s40001-022-00982-8. PMID: 36609359; PMCID: PMC9817311.
34.Zou F, Li X, Yang R, Zhang R, Zhao X. Effects and underlying mechanisms of food polyphenols in treating gouty arthritis: A review on nutritional intake and joint health. J Food Biochem. 2022 Feb;46(2):e14072. doi: 10.1111/jfbc.14072. Epub 2022 Jan 7. PMID: 34997623.
35.Xu X, Qiu H. BRD4 promotes gouty arthritis through MDM2-mediated PPARγ degradation and pyroptosis. Mol Med. 2024 May 21;30(1):67. doi: 10.1186/s10020-024-00831-w. PMID: 38773379; PMCID: PMC11110350.
Published
2025/10/30
Section
Original paper