2024-03-29T08:45:43Zhttps://eprints.lib.hokudai.ac.jp/dspace-oai/requestoai:eprints.lib.hokudai.ac.jp:2115/799222022-11-17T02:08:08Zhdl_2115_20048hdl_2115_140Effects of pentosan polysulfate on cell proliferation, cell cycle progression and cyclin-dependent kinases expression in canine articular chondrocytesAkaraphutiporn, EkkapolBwalya, Eugene C.Kim, SanghoSunaga, TakafumiEchigo, RyosukeOkumura, Masahiroarticular chondrocytecell cyclecyclin-dependent kinasesosteoarthritispentosan polysulfate649Pentosan polysulfate (PPS) is a semi-synthetic sulfated polysaccharide compound which has been shown the benefits on therapeutic treatment for osteoarthritis (OA) and has been proposed as a disease modifying osteoarthritis drugs (DMOADs). This study investigated the effects of PPS on cell proliferation, particularly in cell cycle modulation and phenotype promotion of canine articular chondrocytes (AC). Canine AC were treated with PPS (0-80 mu g/ml) for 24, 48 and 72 hr. The effect of PPS on cell viability, cell proliferation and cell cycle distribution were analyzed by MTT assay, DNA quantification and flow cytometry. Chondrocyte phenotype was analyzed by quantitative real-time PCR (qPCR) and glycosaminoglycan (GAG) quantification. PPS significantly reduced AC proliferation through cell cycle modulation particularly by maintaining a significantly higher proportion of chondrocytes in the G1 phase and a significantly lower proportion in the S phase of the cell cycle in a concentration- and time-dependent manner. While the proportion of chondrocytes in G1 phase corresponded with the significant downregulation of cyclin-dependent kinase (CDK) 1 and 4. Furthermore, the study confirms that PPS promotes a chondrogenic phenotype of AC through significant upregulation of collagen type II (Col2A1) mRNA and GAG synthesis. The effect of PPS on the inhibition of chondrocyte proliferation while promoting a chondrocyte phenotype could be beneficial in the early stages of OA treatment, which transient increase in proliferative activity of chondrocytes with subsequent phenotypic shift and less productive in an essential component of extracellular matrix (ECM) is observed.公益社団法人 日本獣医学会 (The Japanese Society of Veterinary Science)Journal Articlehttp://hdl.handle.net/2115/799220916-7250Journal of veterinary medical science828120912182020-08enginfo:doi/10.1292/jvms.20-0091none