Xiaohua Chen, Feng He, Hongyun Zhang, Yuanjun Ma, Jia Yu, Han Qin, Fan Wu, Zhuo Wang, Ying Zhan, Jing Zhang, Lei Lu, Mian Zhang, Shibin Yu
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SDC4 conditional knockout (SDC4-cKO) and Sdc4<sup>flox/flox</sup> mice were induced TMJOA. Cartilage degeneration was assessed using haematoxylin & eosin (H&E) and safranin O (SO) staining. Protein levels of SDC4, matrix metalloproteinases (MMPs), a disintegrin and metalloproteinase with a thrombospondin motifs 5 (ADAMTS5), tumour necrosis factor α (TNFα), type II collagen (Col-II), aggrecan (ACAN), cleaved caspase 3 (CASP3), Ki67 and related pathways in condylar cartilage were evaluated by immunohistochemical (IHC) staining or western blot assays.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>SDC4 expression was evidently increased in MIA-model animals compared to control groups. rrIL-1β stimulation increased the expression of SDC4, MMP3 and ADAMTS5 expression in chondrocytes, while decreasing the expression of Col-II. These effects were reversed by si-SDC4 in vitro. In vivo, SDC4 blockade reduced the death of chondrocytes and the loss of cartilage matrix, which was evidenced by increased expression of Col-II and ACAN, and a decrease in SDC4, MMP13 and cleaved-CASP3-positive cells. Furthermore, the protein levels of ACAN and Ki67 were elevated, and the ERK1/2 and P38 signalling pathways were activated following SDC4 inhibition.</p>\n </section>\n \n <section>\n \n <h3> Conclusions</h3>\n \n <p>SDC4 inhibition significantly ameliorates condylar cartilage degeneration, which was mediated, at least partly, through P38 and ERK1/2 signalling. Inhibition of SDC4 may be of great value for the treatment of TMJOA.</p>\n </section>\n </div>","PeriodicalId":16605,"journal":{"name":"Journal of oral rehabilitation","volume":"51 11","pages":"2324-2335"},"PeriodicalIF":3.1000,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/joor.13829","citationCount":"0","resultStr":"{\"title\":\"Syndecan-4 inhibition attenuates cartilage degeneration in temporomandibular joint osteoarthritis\",\"authors\":\"Xiaohua Chen, Feng He, Hongyun Zhang, Yuanjun Ma, Jia Yu, Han Qin, Fan Wu, Zhuo Wang, Ying Zhan, Jing Zhang, Lei Lu, Mian Zhang, Shibin Yu\",\"doi\":\"10.1111/joor.13829\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n \\n <section>\\n \\n <h3> Background</h3>\\n \\n <p>Syndecan 4 (SDC4), a type I transmembrane proteoglycan, serves as a critical link between chondrocytes and the extracellular matrix.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Objective</h3>\\n \\n <p>This study aimed to explore the role of SDC4 in cartilage degeneration of temporomandibular joint osteoathritis (TMJOA).</p>\\n </section>\\n \\n <section>\\n \\n <h3> Methods</h3>\\n \\n <p>Condylar chondrocytes were stimulated with varying concentrations of recombinant rat interleukin-1β (rrIL-1β) and SDC4 small interfering RNA (si-SDC4). Anti-SDC4 ectodomain-specific antibodies or IgG were intra-articularly administrated in a TMJOA model rats. SDC4 conditional knockout (SDC4-cKO) and Sdc4<sup>flox/flox</sup> mice were induced TMJOA. Cartilage degeneration was assessed using haematoxylin & eosin (H&E) and safranin O (SO) staining. Protein levels of SDC4, matrix metalloproteinases (MMPs), a disintegrin and metalloproteinase with a thrombospondin motifs 5 (ADAMTS5), tumour necrosis factor α (TNFα), type II collagen (Col-II), aggrecan (ACAN), cleaved caspase 3 (CASP3), Ki67 and related pathways in condylar cartilage were evaluated by immunohistochemical (IHC) staining or western blot assays.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Results</h3>\\n \\n <p>SDC4 expression was evidently increased in MIA-model animals compared to control groups. rrIL-1β stimulation increased the expression of SDC4, MMP3 and ADAMTS5 expression in chondrocytes, while decreasing the expression of Col-II. 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Syndecan-4 inhibition attenuates cartilage degeneration in temporomandibular joint osteoarthritis
Background
Syndecan 4 (SDC4), a type I transmembrane proteoglycan, serves as a critical link between chondrocytes and the extracellular matrix.
Objective
This study aimed to explore the role of SDC4 in cartilage degeneration of temporomandibular joint osteoathritis (TMJOA).
Methods
Condylar chondrocytes were stimulated with varying concentrations of recombinant rat interleukin-1β (rrIL-1β) and SDC4 small interfering RNA (si-SDC4). Anti-SDC4 ectodomain-specific antibodies or IgG were intra-articularly administrated in a TMJOA model rats. SDC4 conditional knockout (SDC4-cKO) and Sdc4flox/flox mice were induced TMJOA. Cartilage degeneration was assessed using haematoxylin & eosin (H&E) and safranin O (SO) staining. Protein levels of SDC4, matrix metalloproteinases (MMPs), a disintegrin and metalloproteinase with a thrombospondin motifs 5 (ADAMTS5), tumour necrosis factor α (TNFα), type II collagen (Col-II), aggrecan (ACAN), cleaved caspase 3 (CASP3), Ki67 and related pathways in condylar cartilage were evaluated by immunohistochemical (IHC) staining or western blot assays.
Results
SDC4 expression was evidently increased in MIA-model animals compared to control groups. rrIL-1β stimulation increased the expression of SDC4, MMP3 and ADAMTS5 expression in chondrocytes, while decreasing the expression of Col-II. These effects were reversed by si-SDC4 in vitro. In vivo, SDC4 blockade reduced the death of chondrocytes and the loss of cartilage matrix, which was evidenced by increased expression of Col-II and ACAN, and a decrease in SDC4, MMP13 and cleaved-CASP3-positive cells. Furthermore, the protein levels of ACAN and Ki67 were elevated, and the ERK1/2 and P38 signalling pathways were activated following SDC4 inhibition.
Conclusions
SDC4 inhibition significantly ameliorates condylar cartilage degeneration, which was mediated, at least partly, through P38 and ERK1/2 signalling. Inhibition of SDC4 may be of great value for the treatment of TMJOA.
期刊介绍：
Journal of Oral Rehabilitation aims to be the most prestigious journal of dental research within all aspects of oral rehabilitation and applied oral physiology. It covers all diagnostic and clinical management aspects necessary to re-establish a subjective and objective harmonious oral function.
Oral rehabilitation may become necessary as a result of developmental or acquired disturbances in the orofacial region, orofacial traumas, or a variety of dental and oral diseases (primarily dental caries and periodontal diseases) and orofacial pain conditions. As such, oral rehabilitation in the twenty-first century is a matter of skilful diagnosis and minimal, appropriate intervention, the nature of which is intimately linked to a profound knowledge of oral physiology, oral biology, and dental and oral pathology.
The scientific content of the journal therefore strives to reflect the best of evidence-based clinical dentistry. Modern clinical management should be based on solid scientific evidence gathered about diagnostic procedures and the properties and efficacy of the chosen intervention (e.g. material science, biological, toxicological, pharmacological or psychological aspects). The content of the journal also reflects documentation of the possible side-effects of rehabilitation, and includes prognostic perspectives of the treatment modalities chosen.
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