Genetic inactivation of ZCCHC6 suppresses IL-6 expression and reduces the severity of experimental osteoarthritis in mice.

Title

Genetic inactivation of ZCCHC6 suppresses IL-6 expression and reduces the severity of experimental osteoarthritis in mice.

Creator

Ansari Mohammad Y; Khan Nazir M; Ahmad Nashrah; Green Jonathan; Novak Kimberly; Haqqi Tariq M

Publisher

Arthritis & rheumatology (Hoboken, N.J.)

Date

2018
2018-10

Description

OBJECTIVE: Cytokine expression is tightly regulated post-transcriptionally but high levels of IL-6 in osteoarthritis (OA) indicate disruption of regulatory mechanisms. ZCCHC6 enzyme is implicated in post-transcriptional regulation of inflammatory cytokine expression but its role in OA pathogenesis is unknown. Here we studied whether ZCCHC6 directs the expression of IL-6 and influence OA pathogenesis in vivo. METHODS: Human and mouse chondrocytes were stimulated with recombinant IL-1beta. We knocked down the expression of ZCCHC6 in human chondrocytes by siRNAs. IL-6 transcript stability was determined by Actinomycin-D chase and 3'-uridylation of miRNAs was determined by deep sequencing. Zcchc6-/- mice were produced by gene targeting. OA was surgically induced in the knee joints of mice and the disease severity was scored using a semi-quantitative scoring system. RESULTS: ZCCHC6 was markedly upregulated in the damaged cartilage from human OA patients and from wild type mice with surgically-induced OA. Overexpression of ZCCHC6 induced the expression of IL-6 and its knockdown reduced the IL-6 transcript stability and IL-1beta-induced expression in chondrocytes. Reintroduction of Zcchc6 in Zcchc6-/- chondrocytes rescued the IL-1beta-induced

Identifier

Rights

Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).

Citation

Ansari Mohammad Y; Khan Nazir M; Ahmad Nashrah; Green Jonathan; Novak Kimberly; Haqqi Tariq M, “Genetic inactivation of ZCCHC6 suppresses IL-6 expression and reduces the severity of experimental osteoarthritis in mice.,” NEOMED Bibliography Database, accessed June 18, 2021, https://neomed.omeka.net/items/show/2984.

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