SP1‑mediated ADAMTS5 transcription promotes IL‑1&beta;‑induced chondrocyte injury via Wnt/&beta;‑catenin pathway in osteoarthritis

Hao,Xiaoting; Wu,Xiaxia

doi:10.3892/mmr.2024.13273

SP1‑mediated ADAMTS5 transcription promotes IL‑1β‑induced chondrocyte injury via Wnt/β‑catenin pathway in osteoarthritis

Authors:
- Xiaoting Hao
- Xiaxia Wu
View Affiliations

Affiliations: Department of Teaching Administration, Xiangyang No. 1 People's Hospital, Hubei University of Medicine, Xiangyang, Hubei 441000, P.R. China, Department of Radiology, Xiangyang No. 1 People's Hospital, Hubei University of Medicine, Xiangyang, Hubei 441000, P.R. China
Published online on: June 26, 2024 https://doi.org/10.3892/mmr.2024.13273
Article Number: 149
Copyright: © Hao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Osteoarthritis (OA) is a chronic disease that involves chondrocyte injury. ADAMTS5 has been confirmed to mediate chondrocyte injury and thus regulate OA progression, but its underlying molecular mechanisms remain unclear. In the present study, interleukin‑1β (IL‑1β)‑induced chondrocytes were used to mimic OA in vitro. Cell proliferation and apoptosis were assessed by MTT assay, EdU assay and flow cytometry, and protein levels of ADAMTS5, specificity protein 1 (SP1), matrix‑related markers and Wnt/β‑catenin pathway‑related markers were examined using western blotting. In addition, ELISA was performed to measure the concentrations of inflammation factors, and oxidative stress was evaluated by detecting SOD activity and MDA levels. The mRNA expression levels of ADAMTS5 and SP1 were determined by reverse transcription‑quantitative PCR, and the interaction between SP1 and ADAMTS5 was analyzed using a dual‑luciferase reporter assay and chromatin immunoprecipitation assay. IL‑1β suppressed proliferation, but promoted apoptosis, extracellular matrix degradation, inflammation and oxidative stress in chondrocytes. ADAMTS5 was upregulated in IL‑1β‑induced chondrocytes, and its knockdown alleviated IL‑1β‑induced chondrocyte injury. SP1 could bind to the ADAMTS5 promoter region to promote its transcription, and SP1 knockdown relieved IL‑1β‑induced chondrocyte injury by reducing ADAMTS5 expression. The SP1/ADAMTS5 axis activated the Wnt/β‑catenin pathway, and the Wnt/β‑catenin pathway agonist, SKL2001, reversed the protective effect of ADAMTS5 knockdown on chondrocyte injury induced by IL‑1β. To the best of our knowledge, the present study was the first to reveal the interaction between SP1 and ADAMTS5 in OA progression and indicated that the SP1/ADAMTS5 axis mediates OA progression by regulating the Wnt/β‑catenin pathway.

View Figures

View References

1	Pereira D, Ramos E and Branco J: Osteoarthritis. Acta Med Port. 28:99–106. 2015. View Article : Google Scholar : PubMed/NCBI
2	Abramoff B and Caldera FE: Osteoarthritis: Pathology, diagnosis, and treatment options. Med Clin North Am. 104:293–311. 2020. View Article : Google Scholar : PubMed/NCBI
3	Schulze-Tanzil G: Activation and dedifferentiation of chondrocytes: Implications in cartilage injury and repair. Ann Anat. 191:325–338. 2009. View Article : Google Scholar : PubMed/NCBI
4	Shen H, He Y, Wang N, Fritch MR, Li X, Lin H and Tuan RS: Enhancing the potential of aged human articular chondrocytes for high-quality cartilage regeneration. FASEB J. 35:e214102021. View Article : Google Scholar : PubMed/NCBI
5	Mao H, Han B, Li H, Tao Y and Wu W: FABP4 knockdown suppresses inflammation, apoptosis and extracellular matrix degradation in IL-1β-induced chondrocytes by activating PPARγ to regulate the NF-κB signaling pathway. Mol Med Rep. 24:8552021. View Article : Google Scholar : PubMed/NCBI
6	Zahan OM, Serban O, Gherman C and Fodor D: The evaluation of oxidative stress in osteoarthritis. Med Pharm Rep. 93:12–22. 2020.PubMed/NCBI
7	Jin J, Lv X, Wang B, Ren C, Jiang J, Chen H, Chen X, Gu M, Pan Z, Tian N, et al: Limonin Inhibits IL-1β-induced inflammation and catabolism in chondrocytes and ameliorates osteoarthritis by activating Nrf2. Oxid Med Cell Longev. 2021:72925122021. View Article : Google Scholar : PubMed/NCBI
8	Wei J, Gao C, Hu K, Li M, Li J, Shen M and Zhang S: Knockdown of DAPK1 attenuates IL-1β-induced extracellular matrix degradation and inflammatory response in osteoarthritis chondrocytes via regulating the p38 MAPK-signaling pathway. Allergol Immunopathol (Madr). 50:169–175. 2022. View Article : Google Scholar : PubMed/NCBI
9	Mead TJ and Apte SS: ADAMTS proteins in human disorders. Matrix Biol. 71–72. 225–239. 2018.
10	Li T, Peng J, Li Q, Shu Y, Zhu P and Hao L: The mechanism and role of ADAMTS protein family in osteoarthritis. Biomolecules. 12:9592022. View Article : Google Scholar : PubMed/NCBI
11	Chu X, You H, Yuan X, Zhao W, Li W and Guo X: Protective effect of lentivirus-mediated siRNA targeting ADAMTS-5 on cartilage degradation in a rat model of osteoarthritis. Int J Mol Med. 31:1222–1228. 2013. View Article : Google Scholar : PubMed/NCBI
12	Glasson SS, Askew R, Sheppard B, Carito B, Blanchet T, Ma HL, Flannery CR, Peluso D, Kanki K, Yang Z, et al: Deletion of active ADAMTS5 prevents cartilage degradation in a murine model of osteoarthritis. Nature. 434:644–648. 2005. View Article : Google Scholar : PubMed/NCBI
13	Liu C, Ren S, Zhao S and Wang Y: LncRNA MALAT1/MiR-145 Adjusts IL-1β-induced chondrocytes viability and cartilage matrix degradation by regulating ADAMTS5 in human osteoarthritis. Yonsei Med J. 60:1081–1092. 2019. View Article : Google Scholar : PubMed/NCBI
14	Yu Z, Cong F, Zhang W, Song T, Zhang S and Jiang R: Circular RNA circ_0020014 contributes to osteoarthritis progression via miR-613/ADAMTS5 axis. Bosn J Basic Med Sci. 22:716–727. 2022.PubMed/NCBI
15	Li N, Wang Y and Wu X: Knockdown of Circ_0037658 alleviates IL-1β-induced osteoarthritis progression by serving as a sponge of miR-665 to regulate ADAMTS5. Front Genet. 13:8868982022. View Article : Google Scholar : PubMed/NCBI
16	Yang Y, Wang Y, Jia H, Li B, Xing D and Li JJ: MicroRNA-1 modulates chondrocyte phenotype by regulating FZD7 of Wnt/β-catenin signaling pathway. Cartilage. 13 (2_Suppl):1019S–1029S. 2021. View Article : Google Scholar : PubMed/NCBI
17	Hu L, Luo D, Zhang H and He L: Polydatin inhibits IL-1β-mediated chondrocyte inflammation and ameliorates cartilage degradation: Involvement of the NF-κB and Wnt/β-catenin pathways. Tissue Cell. 78:1018652022. View Article : Google Scholar : PubMed/NCBI
18	O'Connor L, Gilmour J and Bonifer C: The role of the ubiquitously expressed transcription factor Sp1 in tissue-specific transcriptional regulation and in disease. Yale J Biol Med. 89:513–525. 2016.PubMed/NCBI
19	Shelake S, Sankpal UT, Paul Bowman W, Wise M, Ray A and Basha R: Targeting specificity protein 1 transcription factor and survivin using tolfenamic acid for inhibiting Ewing sarcoma cell growth. Invest New Drugs. 35:158–165. 2017. View Article : Google Scholar : PubMed/NCBI
20	Wong CF, Barnes LM, Dahler AL, Smith L, Popa C, Serewko-Auret MM and Saunders NA: E2F suppression and Sp1 overexpression are sufficient to induce the differentiation-specific marker, transglutaminase type 1, in a squamous cell carcinoma cell line. Oncogene. 24:3525–3534. 2005. View Article : Google Scholar : PubMed/NCBI
21	Li Y, Xie W, Zheng Y, Li H, Wen Z, Wang C, Chen S and Deng Z: The miR-548d-5p/SP1 signaling axis regulates chondrocyte proliferation and inflammatory responses in osteoarthritis. Int Immunopharmacol. 110:1090292022. View Article : Google Scholar : PubMed/NCBI
22	He W, Lin X and Chen K: Specificity protein 1-mediated ACSL4 transcription promoted the osteoarthritis progression through suppressing the ferroptosis of chondrocytes. J Orthop Surg Res. 18:1882023. View Article : Google Scholar : PubMed/NCBI
23	Barra GB, Santa Rita TH, Almeida ALSC, Jácomo RH and Nery LFA: Serum Has higher proportion of Janus kinase 2 V617F Mutation compared to paired EDTA-whole blood sample: A model for somatic mutation quantification using qPCR and the 2^−∆∆Cq method. Diagnostics (Basel). 10:1532020. View Article : Google Scholar : PubMed/NCBI
24	Ebell MH: Osteoarthritis: Rapid evidence review. Am Fam Physician. 97:523–526. 2018.PubMed/NCBI
25	Zhu N, Zhang P, Du L, Hou J and Xu B: Identification of key genes and expression profiles in osteoarthritis by co-expressed network analysis. Comput Biol Chem. 85:1072252020. View Article : Google Scholar : PubMed/NCBI
26	Fisch KM, Gamini R, Alvarez-Garcia O, Akagi R, Saito M, Muramatsu Y, Sasho T, Koziol JA, Su AI and Lotz MK: Identification of transcription factors responsible for dysregulated networks in human osteoarthritis cartilage by global gene expression analysis. Osteoarthritis Cartilage. 26:1531–1538. 2018. View Article : Google Scholar : PubMed/NCBI
27	Huang PY, Wu JG, Gu J, Zhang TQ, Li LF, Wang SQ and Wang M: Bioinformatics analysis of miRNA and mRNA expression profiles to reveal the key miRNAs and genes in osteoarthritis. J Orthop Surg Res. 16:632021. View Article : Google Scholar : PubMed/NCBI
28	Yang CY, Chanalaris A and Troeberg L: ADAMTS and ADAM metalloproteinases in osteoarthritis-looking beyond the ‘usual suspects’. Osteoarthritis Cartilage. 25:1000–1009. 2017. View Article : Google Scholar : PubMed/NCBI
29	Sun K, Luo J, Jing X, Xiang W, Guo J, Yao X, Liang S, Guo F and Xu T: Hyperoside ameliorates the progression of osteoarthritis: An in vitro and in vivo study. Phytomedicine. 80:1533872021. View Article : Google Scholar : PubMed/NCBI
30	Li G, Luo H, Ding Z, Liang H, Lai Z, Chen S and Huang Y: Silencing of circ_0000205 mitigates interleukin-1β-induced apoptosis and extracellular matrix degradation in chondrocytes via targeting miR-766-3p/ADAMTS5 axis. Innate Immun. 28:79–90. 2022. View Article : Google Scholar : PubMed/NCBI
31	Kaczynski J, Cook T and Urrutia R: Sp1- and Kruppel-like transcription factors. Genome Biol. 4:2062003. View Article : Google Scholar : PubMed/NCBI
32	Kong LM, Liao CG, Fei F, Guo X, Xing JL and Chen ZN: Transcription factor Sp1 regulates expression of cancer- associated molecule CD147 in human lung cancer. Cancer Sci. 101:1463–1470. 2010. View Article : Google Scholar : PubMed/NCBI
33	Xu K, Wang X, Zhang Q, Liang A, Zhu H, Huang D, Li C and Ye W: Sp1 downregulates proinflammatory cytokine-induced catabolic gene expression in nucleus pulposus cells. Mol Med Rep. 14:3961–3968. 2016. View Article : Google Scholar : PubMed/NCBI
34	Zhou Y, Wang T, Hamilton JL and Chen D: Wnt/β-catenin signaling in osteoarthritis and in other forms of arthritis. Curr Rheumatol Rep. 19:532017. View Article : Google Scholar : PubMed/NCBI
35	Liu X, Wang L, Ma C, Wang G, Zhang Y and Sun S: Exosomes derived from platelet-rich plasma present a novel potential in alleviating knee osteoarthritis by promoting proliferation and inhibiting apoptosis of chondrocyte via Wnt/β-catenin signaling pathway. J Orthop Surg Res. 14:4702019. View Article : Google Scholar : PubMed/NCBI
36	Zhang Z, Yang P, Wang C and Tian R: LncRNA CRNDE hinders the progression of osteoarthritis by epigenetic regulation of DACT1. Cell Mol Life Sci. 79:4052022. View Article : Google Scholar : PubMed/NCBI