Application of USP10 as diagnostic marker and therapeutic target for rheumatoid arthritis

Abstract

The application belongs to the technical field of biomedicine, and particularly relates to application of USP10 as a diagnostic marker and therapeutic target for rheumatoid arthritis. Experiments prove that the level of USP10 in the synovial tissue, synoviocytes and serum of rheumatoid arthritis patients and other RA involved parts is significantly higher than that of normal people, and USP10 is positively correlated with the occurrence and development of rheumatoid arthritis, and USP10 has the potential to be used as a molecular marker for screening, diagnosis or prognosis evaluation of rheumatoid arthritis. Experiments prove that targeting USP10 can be used as an effective way to treat rheumatoid arthritis. The application has important significance for studying the role of USP10 in rheumatoid arthritis, understanding the mechanism of the disease and developing new treatment strategies.

Description

Technical Field

[0001] This invention belongs to the field of biomedical technology, specifically involving the application of the USP10 gene or USP10 protein as a diagnostic marker and therapeutic target for rheumatoid arthritis. Background Technology

[0002] Rheumatoid arthritis (RA) is a chronic autoimmune disease with an increasing incidence rate. The pathological features of RA are mainly synovial tissue hyperplasia, persistent synovial inflammation, pannus formation, erosion of adjacent articular cartilage and progressive destruction of bone, ultimately leading to joint dysfunction or even loss of function.

[0003] In recent years, with the advancement of technology, our understanding of the pathogenesis of rheumatoid arthritis (RA) has deepened, and fibroblast-like synoviocytes (FLS) have been revealed to play an important role in the pathogenesis of RA. FLS cells proliferate and activate abnormally in the synovium of RA patients, not only participating in local inflammatory responses but also causing damage to surrounding tissues by secreting various cytokines and matrix metalloproteinases, thus accelerating the progression of joint disease.

[0004] Currently, the clinical treatment of rheumatoid arthritis mainly relies on nonsteroidal anti-inflammatory drugs (NSAIDs) and immunosuppressants to control the inflammatory response and slow disease progression. However, these traditional treatments generally suffer from slow onset of action and significant side effects, becoming major challenges in clinical treatment. With the deepening research into the pathological mechanisms of rheumatoid arthritis, early intervention targeting specific molecular targets has become a new research direction. These targeted therapies have shown significant efficacy in patients diagnosed at an early stage, not only effectively controlling disease progression but also significantly improving patient prognosis and quality of life.

[0005] In recent years, autoantibodies such as rheumatoid factor (RF), C-reactive protein (CRP), and anti-cyclic citrullinated peptide antibody (Anti-CCP) have been proposed as diagnostic indicators for rheumatoid arthritis in the laboratory. However, serum tests for these autoantibodies have a certain false-positive rate. Studies have reported that rheumatoid factor may also be present in patients with systemic lupus erythematosus (SLE) and hepatitis C (HCV) infection, leading to a high rate of misdiagnosis. Therefore, relying solely on these indicators is insufficient for a definitive diagnosis of rheumatoid arthritis.

[0006] Several studies have proposed various novel diagnostic biomarkers for rheumatoid arthritis (RA). For example, patent CN113881764A suggests that Jmjd1c gene expression is closely related to rheumatoid arthritis and could serve as a diagnostic biomarker for RA. Patent CN109486942A proposes RPN2 mRNA or RPN2 protein as diagnostic biomarkers for RA. However, these biomarkers are still in the early stages of exploration. Given the complexity of the etiology of RA and the need to improve diagnostic accuracy, there is an urgent need to explore new targets and conduct further experimental research to assist in the definitive diagnosis of rheumatoid arthritis. Summary of the Invention

[0007] One of the objectives of this invention is to provide the application of the USP10 gene or USP10 protein as a molecular marker for screening, diagnosis, or prognostic assessment of rheumatoid arthritis.

[0008] The second objective of this invention is to provide the application of the USP10 gene or USP10 protein in the preparation of products for screening, diagnosis, or prognostic assessment of rheumatoid arthritis.

[0009] Preferably, the product includes reagents and kits.

[0010] A third objective of this invention is to provide a product for screening, diagnosis, or prognostic assessment of rheumatoid arthritis, the product comprising reagents for detecting the mRNA expression level and / or the protein expression level of USP10.

[0011] Preferably, the object to be detected is selected from at least one of the following: peripheral blood, peripheral serum, synovial cells, synovial tissue, bone tissue, or synovial fluid in the joint cavity.

[0012] Preferably, when the test results show that the mRNA expression level and / or protein expression level of USP10 is significantly higher than the preset threshold of the healthy control group, it indicates that the subject being tested has a risk of rheumatoid arthritis and needs to be further diagnosed in combination with other clinical indicators.

[0013] This invention also provides the application of the USP10 gene as a therapeutic target for rheumatoid arthritis, and inhibiting the expression of the USP10 gene can be used to treat rheumatoid arthritis.

[0014] Therefore, the fourth objective of this invention is to provide the application of reagents that inhibit USP10 gene expression in the preparation of drugs for treating rheumatoid arthritis.

[0015] Preferably, the reagent for inhibiting USP10 gene expression includes an RNA interference molecule that targets the USP10 gene.

[0016] Preferably, the RNA interference molecule targeting the USP10 gene is siRNA or shRNA.

[0017] Preferably, the RNA interference molecule targeting the USP10 gene is a double-stranded siRNA, whose sense strand sequence and antisense strand sequence are shown in SEQ ID NO:1 and SEQ ID NO:2, respectively, and / or in SEQ ID NO:1 and SEQ ID NO:2, respectively.

[0018] Compared with the prior art, the beneficial effects of the present invention are as follows: USP10 (Ubiquitin-specific peptidase 10) is an important member of the deubiquitinating enzyme (DUB) family. This enzyme mainly regulates inflammatory responses, cell proliferation, apoptosis, and DNA damage repair through ubiquitin-dependent protein catabolism and the ubiquitin cycle. Aberrant expression of USP10 is associated with a variety of diseases, especially playing an important role in tumors, cystic fibrosis, and metabolic diseases.

[0019] In existing technologies, USP5, USP48, and USP7 have been reported to be associated with inflammation, and some have even suggested their potential as biomarkers for rheumatoid arthritis. However, the known functions of USP10 are currently limited to regulating p53 stability, autophagy, and metabolic stress responses (e.g., through the AMPK pathway), and its direct association with arthritis has not yet been revealed. More importantly, the USP family members exhibit low sequence homology (typically below 30%) and significant differences in substrate-binding domain structures, leading to highly differentiated biological functions and even antagonistic effects. Therefore, those skilled in the art cannot infer the specific role of USP10 in inflammation from the functions of other USP members, let alone anticipate its unique value as a molecular biomarker for rheumatoid arthritis.

[0020] The applicant experimentally discovered and confirmed that the upregulation of USP10 expression in RA was significantly superior to other USP family members in both magnitude and specificity. By systematically comparing the expression levels of multiple inflammation-related genes in the USP family in the same RA and OA patient samples, the applicant found that USP10 expression in RA synovial tissue was upregulated 2.9-fold compared to the OA group, a significantly higher upregulation than other differentially expressed USP genes (which only increased by 1.4-2.4 times). More importantly, USP10 expression was also significantly upregulated in the peripheral blood of RA patients (P<0.01) and strongly positively correlated with disease activity (DAS28 score); while most other USP genes showed no significant difference between RA and OA (P>0.05). This comparative result reveals that although a few members of the USP family are upregulated in RA, only USP10 exhibits the most significant and specific upregulation pattern.

[0021] Therefore, given that the levels of USP10 in synovial tissue, synovial cells, and serum of patients with rheumatoid arthritis are significantly higher than those in normal individuals, and the evidence that USP10 is positively correlated with the occurrence and development of rheumatoid arthritis, USP10 has the potential to serve as a molecular marker for screening, diagnosis, or prognostic assessment of rheumatoid arthritis.

[0022] Furthermore, knockdown of USP10 in RA FLS cells showed an inhibitory effect on FLS cell activation and inflammatory response; knockdown of USP10 expression in K / BxN STA mice showed significant reduction in inflammation and symptom relief. Therefore, targeting USP10 may be an effective approach for the treatment of rheumatoid arthritis.

[0023] This application is of great significance for studying the role of USP10 in rheumatoid arthritis, understanding the disease mechanism, and developing new treatment strategies. Attached Figure Description

[0024] Figure 1 The expression of USP10 in the synovial tissue of KRN serum-induced arthritis mice (KRN STA) and K / BxN serum-induced arthritis mice (K / BxN STA) is shown in Figure A. Figure A shows the inflammatory cell infiltration in the synovial tissue of KRN STA and K / BxN STA mice detected by HE staining, scale bar: 100 μm (20×), 50 μm (63×). Figure B shows the expression of USP10 in the synovial tissue of KRN STA and K / BxN STA mice detected by immunohistochemical staining, scale bar: 100 μm (20×), 50 μm (63×).

[0025] Figures 2-4 This study describes the expression of USP10 in the synovial tissue of patients with osteoarthritis (OA) and renal impairment (RA). Data represent three replicates with three samples per group, and are expressed as mean ± standard deviation. P < 0.01, where: Figure 2 Figure A shows the inflammatory cell infiltration in the synovial tissue of OA and RA patients detected by HE staining, and Figure B shows the expression of USP10 in the synovial tissue of OA and RA patients detected by immunohistochemical staining. Scale bar: 100μm (20×), 50μm (63×).

[0026] Figure 3 To detect the expression of USP10 and TNFα in synovial tissue in OA and RA patients using immunofluorescence double staining (IF), scale bar: 100μm (20×), 50μm (63×).

[0027] Figure 4Figure A shows the expression of USP10 in synovial tissue and FLS cells activated with TNFα by Western blot analysis of OA and RA patients; Figure B shows the expression of USP10 mRNA in synovial tissue and FLS cells activated with TNFα by qRT-PCR analysis of OA and RA patients; Figure C shows the expression of USP10 in peripheral blood of normal individuals and RA patients.

[0028] Figure 5 This study investigated the expression of USP family inflammation-related members in the synovial tissue of patients with osteoarthritis (OA) and renal impairment (RA). The figure shows the mRNA expression of USP family inflammation-related members in the synovial tissue of OA and RA patients detected by qRT-PCR. Data represent three replicates with 13 samples per group, expressed as mean ± standard deviation. P < 0.05.

[0029] Figure 6 Correlation analysis of USP10 mRNA expression in peripheral blood mononuclear cells (PBMCs) of newly diagnosed RA patients with RA disease activity.

[0030] Figure 7 Correlation analysis of USP10 mRNA expression in peripheral blood mononuclear cells (PBMCs) of RA patients with inflammatory factors and chemokines.

[0031] Figures 8-9 To demonstrate that knocking down USP10 can inhibit the activation and inflammatory response of FLS cells; data represent three replicates, with three samples per group, and are expressed as mean ± standard deviation; P < 0.01 ## P < 0.01. Where: Figure 8 Figure A shows the migration ability of FLS cells after USP10 knockdown and TNFα activation, as detected by scratch assay (scale bar: 1000 μm); Figure B shows the invasion ability of FLS cells after USP10 knockdown and TNFα activation, as detected by Transwell assay (scale bar: 1000 μm); Figure C shows the protein expression of matrix metalloproteinases in FLS cells after USP10 knockdown and TNFα activation, as detected by Western blot; Figure D shows the expression of matrix metalloproteinase mRNA in FLS cells after USP10 knockdown and TNFα activation, as detected by qRT-PCR.

[0032] Figure 9Figure A shows the protein expression of inflammatory factors in FLS cells after USP10 knockdown and TNFα activation, as detected by Western blot; Figure B shows the expression of inflammatory factors in FLS cells after USP10 knockdown and TNFα activation, as detected by ELISA; Figure C shows the expression of inflammatory factors and chemokine mRNA in FLS cells after USP10 knockdown and TNFα activation, as detected by qRT-PCR.

[0033] Figure 10 To explore Usp10 in vivo F / FColla6α1 Experimental results on the inflammatory response in K / BxN STA mice. Figure A shows a schematic diagram of the mouse model; Figure B shows a visual representation of ankle joint swelling; Figure C shows a representative micro-CT image (scale bar: 1.0 mm); Figure D shows the joint score and swelling degree in mice; Figure E shows the ELISA detection of the effect of USP10 knockdown on the expression of inflammatory factors in the serum of K / BxN STA mice; and the comparison with USP10... F / F +K / BxN STA group comparison: ## P < 0.01. Detailed Implementation

[0034] The technical solution of this application will be described in more detail below with reference to experiments and accompanying drawings.

[0035] Unless otherwise stated, the terms used herein have the meanings commonly understood by those skilled in the art.

[0036] Comparison of abbreviations and full names: FLS cells: fibroblast-like synovial cells.

[0037] HE staining: Hematoxylin-Eosin staining.

[0038] IF: Immunofluorescence.

[0039] IHC: Immunohistochemistry.

[0040] OA: Osteoarthritis.

[0041] RA: Rheumatoid Arthritis.

[0042] RF: Rheumatoid Factor.

[0043] PLT: Platelet.

[0044] USP10: Ubiquitin-specific peptidase 10.

[0045] WBC: White Blood Cell, total number of white blood cells.

[0046] The KRN STA and K / BxN STA mouse models used in this application are serum-induced arthritis mouse models, which can be used as animal models of RA. With the consent of Professors Christophe Benoist and Diane Mathis of Harvard Medical School, KRN mice (transgenic mice carrying specific T-cell receptors) and NOD mice (non-obese diabetic mice) were purchased from Jiangsu Jicui Pharmaceutical Biotechnology Co., Ltd. KRN mice were crossed with NOD mice to obtain K / BxN mice, which were able to spontaneously develop arthritis at 4-5 weeks of age. Serum from 4-5 week old K / BxN mice with spontaneous arthritis was collected and stored at -80 °C for later use.

[0047] 1. Expression of USP10 in synovial tissue of KRN STA and K / BxN STA mice

[0048] KRN STA and K / BxN-STA mouse models were established: Eight-week-old KRN and K / BxN mice were randomly selected, and their serum was collected. 0.1 mL of KRN and K / BxN mouse serum was injected intraperitoneally into 12-week-old C57BL / 6 mice on days 0 and 2, respectively. KRN STA and K / BxN STA mouse models were induced for 10 days starting from the first serum injection. Significant swelling of the ankle joint was observed on day 4, indicating successful model establishment. Mouse ankle joints were extracted using standard methods, embedded in paraffin, and the expression of USP10 in the synovial tissue of KRN STA and K / BxN STA mice was evaluated using immunohistochemistry.

[0049] See Figure 1 HE staining results showed that K / BxN STA mice exhibited significant inflammatory cell infiltration; immunohistochemical results showed that the positive staining degree of the synovial tissue of K / BxN STA mice was significantly higher than that of KRN STA mice, indicating that the expression of USP10 in the synovial tissue of K / BxN STA mice was significantly higher than that of KRN STA mice.

[0050] 2. A study on the difference in USP10 expression in synovial tissue between clinical OA and RA patients.

[0051] Synovial tissues were collected from patients in the Department of Rheumatology at the First Affiliated Hospital of Anhui Medical University (both OA and RA patients with typical clinical manifestations). RNA was extracted using some standard methods, and qRT-PCR was used to evaluate the expression of USP10 mRNA in the synovial tissues of OA and RA patients. Proteins were extracted using some standard methods, embedded in paraffin, and Western blot, qRT-PCR, immunohistochemistry, and immunofluorescence were used to evaluate the expression of USP10 in the synovial tissues of OA and RA patients. RA FLS cells were extracted, isolated, and cultured. After induction with 10 ng / mL TNFα, cells were collected, proteins were extracted, and changes in USP10 expression were detected after 48 h of induction.

[0052] See Figure 2 HE staining results showed that the infiltration of inflammatory cells in the synovial tissue of RA patients was significantly higher than that in OA patients. Immunohistochemical results showed that the degree of positive staining in the synovial tissue of RA patients was significantly higher than that in OA patients, indicating that the expression of USP10 in the synovial tissue of RA patients was significantly higher than that in OA patients.

[0053] like Figure 3 The immunofluorescence results shown in the figure are as follows: green indicates USP10, red indicates TNFα, and merged images are combined. It can be seen that USP10 is highly expressed in the synovial tissue of RA patients and partially co-localizes with TNFα. Western blot results show that the expression of USP10 in the synovial tissue of RA patients is significantly higher than that in OA patients, and its expression is significantly increased after activation by TNFα-induced stimulation. Figure 4 qRT-PCR results showed that USP10 was significantly elevated in the synovial tissue of RA patients, FLS cells activated by TNFα-induced stimulation, and PBMCs of newly diagnosed RA patients. Figure 4 Comparison results between B and C.

[0054] 3. The performance of representative members of the USP family

[0055] To verify the specificity of USP10 upregulation in RA, the mRNA expression levels of several members of the USP family known to be associated with inflammation were systematically examined in the synovial tissues of RA and OA patients under the same experimental conditions. Results are shown below. Figure 5 The results showed that among the USP family genes that were detected to be inflammation-related and showed significant differences, only USP10 showed the most significant RA-specific upregulation: the expression of USP10 in the RA group was 2.9 times higher than that in the OA group, and this upregulation was significantly higher than that of other differentially expressed USP genes (the increase was only between 1.4 and 2.4 times).

[0056] 4. Correlation between USP10 mRNA expression levels in peripheral blood of newly diagnosed RA patients and clinical disease activity and synovial inflammation markers.

[0057] Peripheral blood clinical samples were collected from newly diagnosed RA patients in the Department of Rheumatology and Immunology, First Affiliated Hospital of Anhui Medical University. Peripheral blood mononuclear cells (PBMCs) were extracted, and the expression of USP10 mRNA was analyzed by qRT-PCR to correlate with RA clinical disease activity and synovial inflammatory factors. Clinical disease activity included DAS28 score, rheumatoid factor (RF), white blood cell count (WBC), platelet count (PLT), pain score, and Swollen score. Synovial inflammatory factors included TNFα (tumor necrosis factor-α), IL6 (interleukin-6), IL1β (interleukin-1β), CCL3 (chemokine ligand 3), CXCL8 (CXC chemokine ligand 8), and IL8 (interleukin-8).

[0058] See qRT-PCR results Figure 6 The figure shows the results of DAS28, RF, WBC, PLT, Pain Score, and Swollen Score, which are associated with RA disease activity, in that order. It can be seen that USP10 mRNA expression is positively correlated with all of these indicators and the differences are statistically significant. See also... Figure 7 Correlation analysis with inflammatory factors of RA synovial membrane showed that the expression of USP10 mRNA was positively correlated with TNFα, IL6, IL1β, CCL3, CXCL8 and IL8 and had statistically significant differences.

[0059] 5. In vitro study on the regulatory effect of USP10 on activation response in TNFα-induced FLS cells.

[0060] Synovial tissue was collected from RA patients, and primary RA FLS cells were extracted and cultured. USP10-siRNA was constructed to knock down the expression of USP10 in FLS.

[0061] USP10-siRNA-1-F:GAGGAAUACUUAGGCUUCATT (SEQ ID NO:1); USP10-siRNA-1-R:UGAAGCCUAAGUAUUCCUCTT (SEQ ID NO: 2); USP10-siRNA-2-F:CGAGGAUGAAUGGGAACAATT (SEQ ID NO:3); USP10-siRNA-2-R:UUGUUCCCAUUCAUCCUCGTT (SEQ ID NO: 4).

[0062] After 48 h of induction activation using 10 ng / mL TNFα (simulating the inflammatory microenvironment in RA patients), the migration of FLS cells after USP10 knockdown was evaluated using a scratch assay; the invasion of FLS cells after USP10 knockdown was evaluated using a Transwell assay; total protein and RNA were extracted from the cells, and the expression of matrix metalloproteinases (MMP2, MMP3, and MMP9) in FLS cells after USP10 knockdown was evaluated using Western blot and qRT-PCR experiments.

[0063] Scratch assay results showed that knocking down USP10 significantly inhibited the migration ability of FLS cells. Figure 8 Figure A; Transwell assay results showed that knocking down USP10 significantly inhibited the invasive ability of FLS cells, see Figure A. Figure 8 Figure B in the middle; Western blot results showed that knocking down USP10 significantly inhibited the expression of MMP3 and MMP9 in FLS cells, see Figure B. Figure 8 Figure C; qRT-PCR results showed that knocking down USP10 significantly inhibited the expression of MMP2, MMP3, and MMP9 in FLS cells. Figure 8 Diagram D in the middle.

[0064] 6. In vitro study on the regulatory role of USP10 in inflammatory response in TNFα-induced FLS cells.

[0065] Synovial tissue was collected from RA patients, and primary FLS cells were extracted and cultured. USP10 expression in FLS cells was knocked down using USP10-siRNA small interference. After 48 h of induction activation with 10 ng / mL TNFα (simulating the inflammatory microenvironment in RA patients), cell supernatant was collected, and total cellular protein and RNA were extracted. The expression of inflammatory factors (IL1β, IL6) in FLS cells was evaluated using Western blot, qRT-PCR, and ELISA experiments.

[0066] See Figure 9 Western blot results showed that knocking down USP10 significantly inhibited the secretion of USP10, IL1β, and IL6 in FLS cells. Figure 9 ELISA results showed that knocking down USP10 significantly inhibited the secretion of inflammatory factors (IL1β and IL6) from FLS cells in the cell supernatant. Figure 9The results of qRT-PCR showed that knockdown of USP10 significantly inhibited the secretion of USP10, inflammatory factors (IL1β, IL6, etc.), and chemokines (CCL3, CXCL1, etc.) in FLS cells. Figure 9 C.

[0067] 7. In vivo study on the regulatory effect of USP10 on inflammatory response in arthritic mice.

[0068] Reference Figure 10 In the construction of synovial cell-specific knockout USP10 gene mice: At 12 weeks of age, mice were randomly divided into two groups: a control group (Usp10...) and a control group (Usp10...). F / F +K / BxN STA) and experimental group (Usp10) F / FCol6α1 A USP10 knockdown model of arthritis was induced in mice by intraperitoneal injection of K / BxN STA mice serum for 10 days. After modeling, ankle swelling was observed and photographed. During the modeling period, ankle swelling and joint swelling scores were recorded every two days to reflect the inflammatory response of USP10 knockdown in arthritis mice. After modeling, mouse serum was collected, and the expression of inflammatory factors (IL1β, IL6, and TNFα) in the serum was evaluated using ELISA. Ankle joints were collected, and micro-CT was used to evaluate the bone damage caused by USP10 knockdown in arthritis mice.

[0069] Joint swelling score: Forelimb score is 0-3, where 0 is no swelling, 1 is mild redness and swelling, 2 is moderate redness and swelling, and 3 is severe redness and swelling or even deformity; Hindlimb score is 0-4, where 0 is no swelling, 1 is redness without swelling, 2 is mild redness and swelling, 3 is moderate redness and swelling, and 4 is severe redness and swelling or even deformity.

[0070] Swelling measurement: The diameter of each mouse's left and right hind paws was measured 0.5 mm below the ankle joint using calipers. Swelling was measured every 2 days, starting from day 0 of the first immunization. Mice with a clinical score of 1 or higher in one paw were considered to be diseased.

[0071] Figure 10 Image B shows a visual representation of ankle swelling in mice, image C shows a representative micro-CT image, image D shows the ankle swelling score and degree of swelling in mice, and image E shows the effect of USP10 knockdown on the expression of inflammatory factors in the serum of K / BxN STA mice as detected by ELISA. It can be seen that USP10 knockdown significantly alleviates the inflammatory response in mice. Micro-CT results show that the ankle swelling and bone damage in the experimental group were significantly lower than those in the control group.

[0072] The above embodiments are only used to illustrate the technical solutions of the present invention, and are not intended to limit the present invention. Although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that any modifications, equivalent substitutions, and improvements made within the spirit and principles of the present invention should be included within the protection scope of the present invention.

Claims

1. Application of the USP10 gene or USP10 protein as a molecular marker for screening, diagnosis, or prognostic assessment of rheumatoid arthritis.

2. Application of the USP10 gene or USP10 protein in the preparation of products for screening, diagnosis or prognostic assessment of rheumatoid arthritis.

3. The application as described in claim 2, characterized in that, The products include reagents and kits.

4. A product for screening, diagnosing, or assessing the prognosis of rheumatoid arthritis, characterized in that, The product contains reagents for detecting the mRNA expression level and / or the protein expression level of USP10.

5. The product as described in claim 4, characterized in that, The test subject is selected from at least one of the following: peripheral blood, peripheral serum, synovial cells, synovial tissue, bone tissue, or synovial fluid in the joint cavity.

6. The product as described in claim 5, characterized in that, When the test results show that the mRNA expression level and / or protein expression level of USP10 are significantly higher than the preset threshold of the healthy control group, it indicates that the subject being tested has a risk of rheumatoid arthritis.

7. Application of reagents that inhibit USP10 gene expression in the preparation of drugs for treating rheumatoid arthritis.

8. The application as described in claim 7, characterized in that, The reagent that inhibits USP10 gene expression includes an RNA interference molecule that targets the USP10 gene.

9. The application as described in claim 8, characterized in that, The RNA interference molecule targeting the USP10 gene is siRNA or shRNA.

10. The application as described in claim 8, characterized in that, The RNA interference molecule targeting the USP10 gene is a double-stranded siRNA, the sense strand sequence and the antisense strand sequence of which are shown in SEQ ID NO:1 and SEQ ID NO:2 and / or in SEQ ID NO:3 and SEQ ID NO:4, respectively.

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