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Inflammation caused-aggrecan degradation is a critical event in the pathogenesis of osteoarthritis (OA). The aggrecanases like a disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS5) are assumed to be key players in the aggrecan destruction. To develop the comprehensive therapy method for OA, it is essential to elucidate the activation mechanism of ADAMTS5 gene after stimulation of inflammatory cytokines like tumor necrosis factor-α (TNF-α). The cell lines of human chondrosarcoma (OUMS-27) and embryonic kidney (HEK293T) were incubated with tumor necrosis factor-α (TNF-α) for certain time periods, and the expression level of ADAMTS5 was measured in both mRNA and protein levels. Tissue-specific ADAMTS5 activation was founded to be induced after TNF-α treatment. Then, the constructs for the promoter region of ADAMTS5 were prepared and luciferase assay was conducted to understand the involvement mechanism of nuclear factor-kappa beta (NF-ĸβ) in ADAMTS5 activation. It was demonstrated that NF-ĸβ induces the ADAMTS5 expression level by directly binding the promoter region of ADAMTS5. Although the TNF-α blocker is used for OA treatment, the development of a more comprehensive treatment strategy is an urgent need. Our experimental data contributes in terms of selecting NF-ĸβ as a target molecule. Up to date, NF-ĸβ has been proven to involve in the ADAMTS5 up-regulation after several pro-inflammatory cytokines stimulation. In conclusion, our findings make important contributions to the knowledge about the roles of NF-ĸβ in ADAMTS5 activation under inflammatory conditions. So, NF-ĸβ could be considered to be a potential target for OA treatment.

Titel:	NF-ĸβ upregulates ADAMTS5 expression by direct binding after TNF-α treatment in OUMS-27 chondrosarcoma cell line.
Autor/in / Beteiligte Person:	Gun Bilgic, D ; Hatipoglu, OF ; Cigdem, S ; Bilgic, A ; Cora, T
Link:	Zum Volltext
Zeitschrift:	Molecular biology reports, Jg. 47 (2020-06-01), Heft 6, S. 4215-4223
Veröffentlichung:	Dordrecht, Boston, Reidel., 2020
Medientyp:	academicJournal
ISSN:	1573-4978 (electronic)
DOI:	10.1007/s11033-020-05514-3
Schlagwort:	ADAMTS5 Protein genetics ADAMTS5 Protein metabolism Bone Neoplasms genetics Cell Line, Tumor Chondrocytes metabolism Chondrosarcoma genetics HEK293 Cells Humans Interleukin-1beta genetics NF-KappaB Inhibitor alpha biosynthesis NF-KappaB Inhibitor alpha genetics NF-KappaB Inhibitor alpha metabolism NF-kappa B genetics Osteoarthritis genetics Signal Transduction Transcriptional Activation drug effects ADAMTS5 Protein biosynthesis Bone Neoplasms metabolism Chondrosarcoma metabolism NF-kappa B metabolism Tumor Necrosis Factor-alpha pharmacology
Sonstiges:	Nachgewiesen in: MEDLINE Sprachen: English Publication Type: Journal Article Language: English [Mol Biol Rep] 2020 Jun; Vol. 47 (6), pp. 4215-4223. <i>Date of Electronic Publication: </i>2020 May 15. MeSH Terms: ADAMTS5 Protein / biosynthesis ; Bone Neoplasms / metabolism ; Chondrosarcoma / metabolism ; NF-kappa B / metabolism ; Tumor Necrosis Factor-alpha / *pharmacology ; ADAMTS5 Protein / genetics ; ADAMTS5 Protein / metabolism ; Bone Neoplasms / genetics ; Cell Line, Tumor ; Chondrocytes / metabolism ; Chondrosarcoma / genetics ; HEK293 Cells ; Humans ; Interleukin-1beta / genetics ; NF-KappaB Inhibitor alpha / biosynthesis ; NF-KappaB Inhibitor alpha / genetics ; NF-KappaB Inhibitor alpha / metabolism ; NF-kappa B / genetics ; Osteoarthritis / genetics ; Signal Transduction ; Transcriptional Activation / drug effects References: Bannuru RR, Schmid CH, Kent DM, Vaysbrot EE, Wong JB, McAlindon TE (2015) Comparative effectiveness of pharmacologic interventions for knee osteoarthritis: a systematic review and network meta-analysis. Ann Intern Med 162(1):46–54. https://doi.org/10.7326/M14-1231. 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Int J Mol Med 27(1):71–78. https://doi.org/10.3892/ijmm.2010.549. (PMID: 10.3892/ijmm.2010.54921069255) Grant Information: 112S611 Türkiye Bilimsel ve Teknolojik Araştirma Kurumu Contributed Indexing: Keywords: ADAMTS5; Inflammation; NF-ĸβ; Osteoarthritis Substance Nomenclature: 0 (Interleukin-1beta) ; 0 (NF-kappa B) ; 0 (Tumor Necrosis Factor-alpha) ; 139874-52-5 (NF-KappaB Inhibitor alpha) ; EC 3.4.24.- (ADAMTS5 Protein) ; EC 3.4.24.- (ADAMTS5 protein, human) Entry Date(s): Date Created: 20200517 Date Completed: 20210216 Latest Revision: 20220311 Update Code: 20231215

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NF-ĸβ upregulates ADAMTS5 expression by direct binding after TNF-α treatment in OUMS-27 chondrosarcoma cell line.