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Anti-arthritic effects of combined treatment with histone deacetylase inhibitor and low-intensity ultrasound in the presence of microbubbles in human rheumatoid synovial cells.
Rheumatology (Oxford). 2008 Apr; 47(4):418-24.R

Abstract

OBJECTIVE

The therapeutic effects of histone deacetylase (HDAC) inhibitor combined with ultrasound (US) (1 MHz, 10% duty factor, 0.1 or 0.2 W/cm(2)) in RA synovial fibroblasts (RASFs) were examined.

METHODS

RASFs were isolated from rheumatoid synovial tissues obtained from patients with RA during total knee arthroplasty. RASFs were treated with an HDAC inhibitor, trichostatin A (TSA), with or without US. Cell viability was estimated using the Trypan blue dye exclusion test and cell cycle was examined by flow cytometry using propidium iodide (PI) staining. Gene expression of cell cycle-related genes cyclin D, cyclin A, cyclin B and p21(WAF1/Cip1) was analysed by semi-quantitative RT-PCR. Detection of apoptosis was examined by flow cytometry using annexin V-FITC and PI staining. Microarray analysis was carried out to profile gene expression of inflammation-related genes.

RESULTS

Dose-dependent decreases in cell viability, cell cycle arrest and apoptosis in RASFs due to TSA were observed. US treatment in the presence of microbubbles increased cellular uptake, but did not induce cell cycle arrest or apoptosis. The combination of TSA and US modulated cell cycle-related gene expression and significantly decreased S phase cells and increased G(2)-M phase cells. US also further enhanced TSA-induced RASF apoptosis and regulated expression of inflammation-related genes.

CONCLUSIONS

HDAC inhibitor in combination with US effectively reduces cell viability and induces apoptosis in RASFs. The combination therapy could be useful to control synovial proliferation and inflammation, since US can be easily applied to targeted joints as local physiotherapy.

Authors+Show Affiliations

Department of Orthopaedic Surgery, Graduate School of Medicine and Pharmaceutical Science, University of Toyama, 2630 Sugitani, Toyama, Toyama 930-0194, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

18281366

Citation

Nakamura, C, et al. "Anti-arthritic Effects of Combined Treatment With Histone Deacetylase Inhibitor and Low-intensity Ultrasound in the Presence of Microbubbles in Human Rheumatoid Synovial Cells." Rheumatology (Oxford, England), vol. 47, no. 4, 2008, pp. 418-24.
Nakamura C, Matsushita I, Kosaka E, et al. Anti-arthritic effects of combined treatment with histone deacetylase inhibitor and low-intensity ultrasound in the presence of microbubbles in human rheumatoid synovial cells. Rheumatology (Oxford). 2008;47(4):418-24.
Nakamura, C., Matsushita, I., Kosaka, E., Kondo, T., & Kimura, T. (2008). Anti-arthritic effects of combined treatment with histone deacetylase inhibitor and low-intensity ultrasound in the presence of microbubbles in human rheumatoid synovial cells. Rheumatology (Oxford, England), 47(4), 418-24. https://doi.org/10.1093/rheumatology/ken003
Nakamura C, et al. Anti-arthritic Effects of Combined Treatment With Histone Deacetylase Inhibitor and Low-intensity Ultrasound in the Presence of Microbubbles in Human Rheumatoid Synovial Cells. Rheumatology (Oxford). 2008;47(4):418-24. PubMed PMID: 18281366.
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TY - JOUR T1 - Anti-arthritic effects of combined treatment with histone deacetylase inhibitor and low-intensity ultrasound in the presence of microbubbles in human rheumatoid synovial cells. AU - Nakamura,C, AU - Matsushita,I, AU - Kosaka,E, AU - Kondo,T, AU - Kimura,T, Y1 - 2008/02/15/ PY - 2008/2/19/pubmed PY - 2008/5/9/medline PY - 2008/2/19/entrez SP - 418 EP - 24 JF - Rheumatology (Oxford, England) JO - Rheumatology (Oxford) VL - 47 IS - 4 N2 - OBJECTIVE: The therapeutic effects of histone deacetylase (HDAC) inhibitor combined with ultrasound (US) (1 MHz, 10% duty factor, 0.1 or 0.2 W/cm(2)) in RA synovial fibroblasts (RASFs) were examined. METHODS: RASFs were isolated from rheumatoid synovial tissues obtained from patients with RA during total knee arthroplasty. RASFs were treated with an HDAC inhibitor, trichostatin A (TSA), with or without US. Cell viability was estimated using the Trypan blue dye exclusion test and cell cycle was examined by flow cytometry using propidium iodide (PI) staining. Gene expression of cell cycle-related genes cyclin D, cyclin A, cyclin B and p21(WAF1/Cip1) was analysed by semi-quantitative RT-PCR. Detection of apoptosis was examined by flow cytometry using annexin V-FITC and PI staining. Microarray analysis was carried out to profile gene expression of inflammation-related genes. RESULTS: Dose-dependent decreases in cell viability, cell cycle arrest and apoptosis in RASFs due to TSA were observed. US treatment in the presence of microbubbles increased cellular uptake, but did not induce cell cycle arrest or apoptosis. The combination of TSA and US modulated cell cycle-related gene expression and significantly decreased S phase cells and increased G(2)-M phase cells. US also further enhanced TSA-induced RASF apoptosis and regulated expression of inflammation-related genes. CONCLUSIONS: HDAC inhibitor in combination with US effectively reduces cell viability and induces apoptosis in RASFs. The combination therapy could be useful to control synovial proliferation and inflammation, since US can be easily applied to targeted joints as local physiotherapy. SN - 1462-0332 UR - https://www.unboundmedicine.com/medline/citation/18281366/Anti_arthritic_effects_of_combined_treatment_with_histone_deacetylase_inhibitor_and_low_intensity_ultrasound_in_the_presence_of_microbubbles_in_human_rheumatoid_synovial_cells_ L2 - https://academic.oup.com/rheumatology/article-lookup/doi/10.1093/rheumatology/ken003 DB - PRIME DP - Unbound Medicine ER -