Journal: Cellular & Molecular Biology Letters

Article Title: CIP2A promotes inflammation and exacerbates osteoarthritis by targeting CEMIP

doi: 10.1186/s11658-025-00748-0

Figure Lengend Snippet: CIP2A expression in OA cartilage and chondrocytes. A Representative images of HE staining of human knee cartilage, n = 6, scale bar = 100 μm. B Representative images of CIP2A-specific IHC staining of human knee cartilage, n = 6, scale scale bar = 100 μm. C Quantitative statistical plot of the ratio of CIP2A-specific IHC staining positive cells in human knee cartilage, n = 6. D Representative images of HE staining of mouse knee joints, n = 6, scale bar = 100 μm. E Representative images of CIP2A-specific IHC staining of mouse knee joints, n = 6, scale bar = 100 μm. F Quantitative statistical plot of the ratio of CIP2A-specific IHC staining positive cells in mouse knee joints, n = 6. G Quantitative reverse transcriptasepolymerase chain reaction (qRT-PCR) statistical plot of CIP2A expression in chondrocytes treated with 5 ng/mL IL-1β for different time points, n = 3. H qRT-PCR statistical plot of CIP2A expression in chondrocytes treated with different concentrations of IL-1β for 24 h, n = 3. I Representative WB results of CIP2A expression in chondrocytes treated with 5 ng/mL IL-1β for different time points, n = 3. J Representative WB results of CIP2A expression in chondrocytes treated with different concentrations of IL-1β for 24 h, n = 3. * P < 0.05, **** P < 0.0001

Article Snippet: The CIP2A inhibitor TD52 was purchased from MedChemExpress (HY-135699, Shanghai, China).

Techniques: Expressing, Staining, Immunohistochemistry, Quantitative RT-PCR

Journal: Cellular & Molecular Biology Letters

Article Title: CIP2A promotes inflammation and exacerbates osteoarthritis by targeting CEMIP

doi: 10.1186/s11658-025-00748-0

Figure Lengend Snippet: Effect of CIP2A on ECM anabolism and catabolism of chondrocytes in vitro. A – F qRT-PCR statistical plots of CIP2A and anabolic–catabolic marker expression in chondrocytes transfected with CIP2A siRNA (si-CIP2A) or scrambled siRNA (si-NC) for 24 h followed by 5 ng/mL IL-1β exposure for 24 h, n = 3. G Representative WB results of CIP2A and anabolic–catabolic marker expression in chondrocytes transfected with si-CIP2A or si-NC for 24 h followed by 5 ng/mL IL-1β exposure for 24 h, n = 3. H – M qRT-PCR statistical plots of CIP2A and anabolic–catabolic marker expression in chondrocytes transfected with CIP2A overexpression plasmid (p-CIP2A) or control empty plasmid (p-NC) for 24 h followed by 5 ng/mL IL-1β exposure for 24 h, n = 3. N Representative WB results of CIP2A and anabolic–catabolic marker expression in chondrocytes transfected with p-CIP2A or p-NC for 24 h followed by 5 ng/mL IL-1β exposure for 24 h, n = 3. * P < 0.05, ** P < 0.01, *** P < 0.001, **** P < 0.0001

Article Snippet: The CIP2A inhibitor TD52 was purchased from MedChemExpress (HY-135699, Shanghai, China).

Techniques: In Vitro, Quantitative RT-PCR, Marker, Expressing, Transfection, Over Expression, Plasmid Preparation, Control

Journal: Cellular & Molecular Biology Letters

Article Title: CIP2A promotes inflammation and exacerbates osteoarthritis by targeting CEMIP

doi: 10.1186/s11658-025-00748-0

Figure Lengend Snippet: Effect of CIP2A on chondrocyte inflammation in vitro and ubiquitination modification of CIP2A. A qRT-PCR statistical plot of inflammation-related factor expression in chondrocytes transfected with si-CIP2A or si-NC for 24 h followed by 5 ng/mL IL-1β exposure for 24 h, n = 3. B qRT-PCR statistical plot of inflammation-related factor expression in chondrocytes transfected with p-CIP2A or p-NC for 24 h followed by 5 ng/mL IL-1β exposure for 24 h, n = 3. C Representative WB results of inflammation-related factor expression in chondrocytes transfected with si-CIP2A or si-NC for 24 h followed by 5 ng/mL IL-1β exposure for 24 h, n = 3. D Representative WB results of inflammation-related factor in chondrocytes transfected with p-CIP2A or p-NC for 24 h followed by 5 ng/mL IL-1β exposure for 24 h, n = 3. E Representative WB results of CIP2A and NF-κB signaling pathway proteins expression in chondrocytes transfected with si-CIP2A or si-NC for 48 h followed by 5 ng/mL IL-1β exposure, n = 3. F – H Quantitative statistical plots of the ratio of phosphorylated proteins to total proteins of NF-κB signaling pathway in chondrocytes transfected with si-CIP2A or si-NC for 48 h followed by 5 ng/mL IL-1β exposure, n = 3. I Representative WB results of CIP2A and NF-κB signaling pathway proteins expression in chondrocytes transfected with p-CIP2A or p-NC for 48 h followed by 5 ng/mL IL-1β exposure, n = 3. J – L Quantitative statistical plots of the ratio of phosphorylated proteins to total proteins of NF-κB signaling pathway in chondrocytes transfected with p-CIP2A or p-NC for 48 h followed by 5 ng/mL IL-1β exposure, n = 3. M Representative WB results of CIP2A expression in chondrocytes treated with MG132 or DMSO for 2 h followed by 5 ng/mL IL-1β exposure for 6 h, n = 3. N Representative WB results of endogenous CoIP validation of CIP2A and Ub interaction in chondrocytes, n = 3. Chondrocytes were treated with MG132 or DMSO for 2 h followed by 5 ng/mL IL-1β exposure for 6 h. O , P Representative WB results of exogenous CoIP validation of CIP2A and K48/K63-Ub interaction in chondrocytes, n = 3. Chondrocytes were transfected with the FLAG-tagged CIP2A overexpression plasmid and HA-tagged K48/K63-Ub overexpression plasmid for 48 h and then treated with MG132 for 2 h followed by 5 ng/mL IL-1β exposure for 6 h. * P < 0.05, ** P < 0.01, *** P < 0.001

Article Snippet: The CIP2A inhibitor TD52 was purchased from MedChemExpress (HY-135699, Shanghai, China).

Techniques: In Vitro, Ubiquitin Proteomics, Modification, Quantitative RT-PCR, Expressing, Transfection, Biomarker Discovery, Over Expression, Plasmid Preparation

Journal: Cellular & Molecular Biology Letters

Article Title: CIP2A promotes inflammation and exacerbates osteoarthritis by targeting CEMIP

doi: 10.1186/s11658-025-00748-0

Figure Lengend Snippet: Effect of CIP2A on OA progression in vivo. CIP2A-targeted adenovirus was injected into the knee-joint cavity of the mouse surgical models for 7 consecutive weeks. A Schematic diagram of animal experiment. B Representative images of HE and SO/FG staining of the knee joints at 8 weeks after surgery, during which Ad-shCIP2A or Ad-shControl was injected once a week, n = 6, scale bar = 100 μm. C Representative micro-CT three-dimensional reconstruction images of knee joints at 8 weeks after surgery, n = 6, scale bar = 1 mm. D Knee OARSI score at 8 weeks after surgery, n = 6. E Knee osteophyte score at 8 weeks after surgery, n = 6. F Representative images of IHC staining of CIP2A, ECM anabolic–catabolic markers, and inflammation-related factors of knee joints at 8 weeks after surgery, n = 6, scale bar = 100 μm. G – L Quantitative statistical plots of IHC staining positive cell ratio of CIP2A, ECM anabolic–catabolic markers, and inflammation-related factors in knee joints at 8 weeks after surgery, n = 6. M Representative images of HE and SO/FG staining of the knee joints at 8 weeks after surgery, during which Ad-CIP2A or Ad-Control was injected once a week, n = 6, scale bar = 100 μm. N Representative micro-CT three-dimensional reconstruction images of knee joints at 8 weeks after surgery, n = 6, scale bar = 1 mm. O Knee OARSI score at 8 weeks after surgery, n = 6. P Knee osteophyte score at 8 weeks after surgery, n = 6. Q Representative images of IHC staining of CIP2A, ECM anabolic–catabolic markers, and inflammation-related factors of knee joints at 8 weeks after surgery, n = 6, scale bar = 100 μm. R – W Quantitative statistical plots of IHC staining positive cell ratio of CIP2A, ECM anabolic–catabolic markers, and inflammation-related factors in knee joints at 8 weeks after surgery, n = 6. * P < 0.05, ** P < 0.01, *** P < 0.001, **** P < 0.0001

Article Snippet: The CIP2A inhibitor TD52 was purchased from MedChemExpress (HY-135699, Shanghai, China).

Techniques: In Vivo, Injection, Staining, Micro-CT, Immunohistochemistry, Control

Journal: Cellular & Molecular Biology Letters

Article Title: CIP2A promotes inflammation and exacerbates osteoarthritis by targeting CEMIP

doi: 10.1186/s11658-025-00748-0

Figure Lengend Snippet: The effect of CIP2A on cartilage is related to its downstream CEMIP. A Heatmap of differential genes identified by RNA-seq of chondrocytes transfected with si-CIP2A or si-NC for 24 h followed by 5 ng/mL IL-1β exposure for 24 h, n = 3. B Volcano plot of differential genes identified by RNA-seq of chondrocytes transfected with si-CIP2A or si-NC for 24 h followed by 5 ng/mL IL-1β exposure for 24 h, n = 3. C Pathway enrichment analysis of RNA-seq of chondrocytes transfected with si-CIP2A or si-NC for 24 h followed by 5 ng/mL IL-1β exposure for 24 h. D NF-κB signaling pathway in GSEA enrichment analysis of RNA-seq of chondrocytes transfected with si-CIP2A or si-NC for 24 h followed by 5 ng/mL IL-1β exposure for 24 h. E Pathway network of RNA-seq of chondrocytes transfected with si-CIP2A or si-NC for 24 h followed by 5 ng/mL IL-1β exposure for 24 h. F Volcano plot of interacting proteins identified by CoIP-MS of chondrocytes transfected with p-CIP2A for 24 h followed by 5 ng/mL IL-1β exposure for 24 h. CIP2A was the target protein. G Network of interaction proteins identified by CoIP-MS of chondrocytes transfected with p-CIP2A for 24 h followed by 5 ng/mL IL-1β exposure for 24 h. CIP2A was the target protein. H Venn diagram depicting overlap of RNA-seq and CoIP-MS results. The Venn diagram was generated using the free online analysis tool OmicShare ( https://www.omicshare.com/tools ). I Representative WB results of endogenous CoIP validation of CIP2A and CEMIP interaction in chondrocytes, n = 3. CIP2A was the target protein of CoIP. J Representative WB results of exogenous CoIP validation of CIP2A and CEMIP interaction in chondrocytes, n = 3. Chondrocytes were transfected with the MYC-tagged CEMIP overexpression plasmid for 24 h and then treated with 5 ng/mL IL-1β for 24 h. CEMIP was the target protein of CoIP. K qRT-PCR statistical plot of CEMIP expression in chondrocytes transfected with si-CIP2A or si-NC for 24 h followed by 5 ng/mL IL-1β exposure for 24 h, n = 3. L qRT-PCR statistical plot of CEMIP expression in chondrocytes transfected with p-CIP2A or p-NC for 24 h followed by 5 ng/mL IL-1β exposure for 24 h, n = 3. M qRT-PCR statistical plot of CEMIP expression in chondrocytes treated with TD52 or DMSO for 24 h followed by 5 ng/mLIL-1β exposure for 24 h, n = 3. N Representative WB results of CEMIP expression in chondrocytes transfected with si-CIP2A or si-NC for 24 h followed by 5 ng/mLIL-1β exposure for 24 h, n = 3. O Representative WB results of CEMIP expression in chondrocytes transfected with p-CIP2A or p-NC for 24 h followed by 5 ng/mL IL-1β exposure for 24 h, n = 3. P Representative WB results of CEMIP expression in chondrocytes treated with TD52 or DMSO for 24 h followed by 5 ng/mL IL-1β exposure for 24 h, n = 3. * P < 0.05, ** P < 0.01, *** P < 0.001, **** P < 0.0001

Article Snippet: The CIP2A inhibitor TD52 was purchased from MedChemExpress (HY-135699, Shanghai, China).

Techniques: RNA Sequencing, Transfection, Generated, Biomarker Discovery, Over Expression, Plasmid Preparation, Quantitative RT-PCR, Expressing

Journal: Cellular & Molecular Biology Letters

Article Title: CIP2A promotes inflammation and exacerbates osteoarthritis by targeting CEMIP

doi: 10.1186/s11658-025-00748-0

Figure Lengend Snippet: Effect of CEMIP on ECM anabolism–catabolism and inflammation of chondrocytes in vitro. A Representative WB results of CEMIP expression in chondrocytes treated with 5 ng/mL IL-1β for different time points, n = 3. B qRT-PCR statistical plot of CEMIP expression in chondrocytes treated with 5 ng/mL IL-1β for different time points, n = 3. C Representative WB results of CEMIP expression in chondrocytes treated with different concentrations of IL-1β for 24 h, n = 3. D qRT-PCR statistical plot of CEMIP expression in chondrocytes treated with different concentrations of IL-1β for 24 h, n = 3. E – K , V qRT-PCR statistical plots of CEMIP, CIP2A, anabolic–catabolic markers, and inflammation-related factors expression in chondrocytes transfected with CEMIP siRNA (si-CEMIP) or scrambled siRNA (si-NC) for 24 h followed by 5 ng/mL IL-1β exposure for 24 h, n = 3. L , U Representative WB results of CEMIP, CIP2A, anabolic–catabolic markers, and inflammation-related factors expression in chondrocytes transfected with si-CEMIP or si-NC for 24 h followed by 5 ng/mL IL-1β exposure for 24 h, n = 3. M – S , X qRT-PCR statistical plots of CEMIP, CIP2A, anabolic–catabolic markers, and inflammation-related factor expression in chondrocytes transfected with CEMIP overexpression plasmid (p-CEMIP) or control empty plasmid (p-NC) for 24 h followed by 5 ng/mL IL-1β exposure for 24 h, n = 3. T , W Representative WB results of CEMIP, CIP2A, anabolic–catabolic markers, and inflammation-related factors expression in chondrocytes transfected with p-CEMIP or p-NC for 24 h followed by 5 ng/mL IL-1β exposure for 24 h, n = 3. Y Representative WB results of CEMIP and NF-κB signaling pathway proteins expression in chondrocytes transfected with p-CEMIP or p-NC for 48 h followed by 5 ng/mL IL-1β exposure, n = 3. Z Quantitative statistical plots of the ratio of phosphorylated proteins to total proteins of NF-κB signaling pathway in chondrocytes transfected with p-CEMIP or p-NC for 48 h followed by 5 ng/mL IL-1β exposure, n = 3. * P < 0.05, ** P < 0.01, *** P < 0.001, **** P < 0.0001

Article Snippet: The CIP2A inhibitor TD52 was purchased from MedChemExpress (HY-135699, Shanghai, China).

Techniques: In Vitro, Expressing, Quantitative RT-PCR, Transfection, Over Expression, Plasmid Preparation, Control

Journal: Cellular & Molecular Biology Letters

Article Title: CIP2A promotes inflammation and exacerbates osteoarthritis by targeting CEMIP

doi: 10.1186/s11658-025-00748-0

Figure Lengend Snippet: CIP2A synergizes with its downstream CEMIP to regulate chondrocytes degeneration and inflammation in vitro. A – H qRT-PCR statistical plots of CIP2A, CEMIP, anabolic–catabolic markers, and inflammation-related factors expression in chondrocytes transfected with si-CIP2A or si-NC with or without p-CEMIP for 24 h followed by 5 ng/mL IL-1β exposure for 24 h, n = 3. I , J Representative WB results of CIP2A, CEMIP, anabolic–catabolic markers, and inflammation-related factors expression in chondrocytes transfected with si-CIP2A or si-NC with or without p-CEMIP for 24 h followed by 5 ng/mLIL-1β exposure for 24 h, n = 3. K – M Representative immunofluorescence images of anabolic–catabolic markers and inflammation-related factors in chondrocytes transfected with si-CIP2A or si-NC with or without p-CEMIP for 24 h followed by 5 ng/mL IL-1β exposure for 24 h, n = 3. N – P Semiquantitative statistical plots of mean fluorescence intensity of immunofluorescence detection of anabolic–catabolic markers and inflammation-related factor expression in chondrocytes transfected with si-CIP2A or si-NC with or without p-CEMIP for 24 h followed by 5 ng/mL IL-1β exposure for 24 h, n = 3. * P < 0.05, ** P < 0.01, *** P < 0.001, **** P < 0.0001

Article Snippet: The CIP2A inhibitor TD52 was purchased from MedChemExpress (HY-135699, Shanghai, China).

Techniques: In Vitro, Quantitative RT-PCR, Expressing, Transfection, Immunofluorescence, Fluorescence

Journal: Cellular & Molecular Biology Letters

Article Title: CIP2A promotes inflammation and exacerbates osteoarthritis by targeting CEMIP

doi: 10.1186/s11658-025-00748-0

Figure Lengend Snippet: Schematic diagram of the role of CIP2A in OA cartilage. In response to stimuli, CIP2A is ubiquitinated and interacts with CEMIP and PP2A. On one hand, the CIP2A/CEMIP/PP2A axis promotes ECM degradation by mediating the disorder of ECM anabolism and catabolism. On the other hand, it activates NF-κB signaling pathway, upregulates proinflammatory factors, and promotes inflammation. CIP2A leads to cartilage destruction and inflammation, accelerating OA. The schematic diagram created with BioRender.com

Article Snippet: The CIP2A inhibitor TD52 was purchased from MedChemExpress (HY-135699, Shanghai, China).

Techniques: