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• W2474059280 abstract "Objective Basic calcium phosphate (BCP) and monosodium urate (MSU) crystals are particulates with potent pro-inflammatory effects, associated with osteoarthritis (OA) and gout, respectively. Bone erosion, due to increased osteoclastogenesis, is a hallmark of both arthropathies and results in severe joint destruction. The aim of this study was to investigate the effect of these endogenous particulates on anti-osteoclastogenic cytokine signalling. Methods Human osteoclast precursors (OcP) were treated with BCP and MSU crystals prior to stimulation with Interleukin (IL-6) or Interferon (IFN-γ) and the effect on Signal Transducer and Activator of Transcription (STAT)-3 and STAT-1 activation in addition to Mitogen Activated Protein Kinase (MAPK) activation was examined by immunoblotting. Crystal-induced suppressor of cytokine signalling (SOCS) protein and SH-2 containing tyrosine phosphatase (SHP) expression was assessed by real-time polymerase chain reaction (PCR) in the presence and absence of MAPK inhibitors. Results Pre-treatment with BCP or MSU crystals for 1 h inhibited IL-6-induced STAT-3 activation in human OcP, while pre-treatment for 3 h inhibited IFN-γ-induced STAT-1 activation. Both crystals activated p38 and extracellular signal–regulated (ERK) MAPKs with BCP crystals also activating c-Jun N-terminal kinase (JNK). Inhibition of p38 counteracted the inhibitory effect of BCP and MSU crystals and restored STAT-3 phosphorylation. In contrast, STAT-1 phosphorylation was not restored by MAPK inhibition. Finally, both crystals potently induced the expression of SOCS-3 in a MAPK dependent manner, while BCP crystals also induced expression of SHP-1 and SHP-2. Conclusion This study provides further insight into the pathogenic effects of endogenous particulates in joint arthropathies and demonstrates how they may contribute to bone erosion via the inhibition of anti-osteoclastogenic cytokine signalling. Potential targets to overcome these effects include p38 MAPK, SOCS-3 and SHP phosphatases." @default.
• W2474059280 created "2016-07-22" @default.
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• W2474059280 date "2016-12-01" @default.
• W2474059280 modified "2023-10-13" @default.
• W2474059280 title "Intra-articular basic calcium phosphate and monosodium urate crystals inhibit anti-osteoclastogenic cytokine signalling" @default.
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• W2474059280 doi "https://doi.org/10.1016/j.joca.2016.07.001" @default.
• W2474059280 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/27426968" @default.
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