|Year : 2022 | Volume
| Issue : 4 | Page : 89-95
The clinical significance of serum complement component 1q tumor necrosis factor-related protein 3 and complement component 1q tumor necrosis factor-related protein 9 levels in patients with rheumatoid arthritis
Xin Li, Yuan Wang, Xiaoxia Jia, Jing Ke, Baoyu Zhang, Yan Wang
Center for Endocrine Metabolism and Immune Diseases, Beijing Luhe Hospital, Capital Medical University, Beijing, China
|Date of Submission||20-Aug-2022|
|Date of Decision||03-Oct-2022|
|Date of Acceptance||17-Oct-2022|
|Date of Web Publication||27-Dec-2022|
MD, Center for Endocrine Metabolism and Immune Diseases, Beijing Luhe Hospital, Capital Medical University, Beijing, 101149
PhD, Center for Endocrine Metabolism and Immune Diseases, Beijing Luhe Hospital, Capital Medical University, Beijing, 101149
Source of Support: None, Conflict of Interest: None
Objective: The objective of this study was to assess the expression of serum complement component 1q tumor necrosis factor-related protein 3 (CTRP3) and CTRP9 in rheumatoid arthritis (RA) patients, and further explore their correlation with disease activity and the predictive value of RA.
Methods: RA group (n = 60) and healthy group (n = 60) were enrolled in Beijing Luhe Hospital, Capital Medical University. We collected the clinical data, including the basic information, laboratory parameters as well as the Disease Activity Score using 28 joint counts (DAS28) scores, and measured the expression of serum CTRP3 and CTRP9 in two groups by enzyme-linked immunosorbent assay. To analyze the correlation between serum CTRP3 and CTRP9 and RA. We explored the predictive value of the serum CTRP3 and CTRP9 for RA.
Results: Compared to the healthy group, the expression of serum CTRP3 and CTRP9 was higher in the RA group (P < 0.05). Except rheumatoid factor (serum CTRP9: r = −0.310, P = 0.018), and immunoglobulin (serum CTRP9: r = 0.338, P = 0.010), platelet, erythrocyte sedimentation rate, C-reactive protein, DAS28, anti-cyclic citrullinated peptide antibody, triglyceride, total cholesterol, high-density lipoprotein, low-density lipoprotein, etc., of RA patients were not related to the levels of serum CTRP3 and CTRP9. The best cutoff value of serum CTRP3 and CTRP9 was 31.66 and 34.39 ng/ml, respectively. In terms of sensitivity, negative predictive value, and accuracy, compared with single detection of serum CTRP3 or CTRP9, combined detection has more predictive value for RA.
Conclusion: CTRP3 and CTRP9 may become two candidate biomarkers for RA. The serum CTRP3 and CTRP9 may have certain predictive values for RA.
Keywords: Complement component 1q tumor necrosis factor-related protein 3, complement component 1q tumor necrosis factor-related protein 9, disease activity, predictive value, rheumatoid arthritis
|How to cite this article:|
Li X, Wang Y, Jia X, Ke J, Zhang B, Wang Y. The clinical significance of serum complement component 1q tumor necrosis factor-related protein 3 and complement component 1q tumor necrosis factor-related protein 9 levels in patients with rheumatoid arthritis. Environ Dis 2022;7:89-95
|How to cite this URL:|
Li X, Wang Y, Jia X, Ke J, Zhang B, Wang Y. The clinical significance of serum complement component 1q tumor necrosis factor-related protein 3 and complement component 1q tumor necrosis factor-related protein 9 levels in patients with rheumatoid arthritis. Environ Dis [serial online] 2022 [cited 2023 Mar 30];7:89-95. Available from: http://www.environmentmed.org/text.asp?2022/7/4/89/365625
| Introduction|| |
Rheumatoid arthritis (RA) is considered an autoimmune disease with synovitis as the main pathological manifestation, characterized by chronic symmetrical polyarthritis. RA has a high disability and mortality rate. Joint malformations, increased incidence of cardiovascular events, and systemic multi-organ involvement seriously affect the quality of life and physical and mental health of RA patients, and cause huge economic burden to society. Therefore, early diagnosis and treatment are extremely important. Biomarkers play an indispensable role in diagnosing, judging disease activity, and predicting the prognosis of RA. Rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPAs), such as anti-cyclic citrullinated peptide (anti-CCP) antibody, anti-mutated citrullinated vimentin (MCV) antibody, antikeratin antibodies (AKAs), and anti-perinuclear factor (APF), detected in serum, are biomarkers for RA. Because of good diagnostic performance, RF and anti-CCP antibody were included in the 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria for RA. RF, a serum biomarker closely related to RA, was detected in 70%–90% of RA patients and 1%–5% of healthy people. Anti-CCP antibody, which can be detected before the clinical manifestations of RA, is used for the early diagnosis of RA. Several studies have shown that the combined detection of RF and anti-CCP antibody can improve the probability of true positivity in the diagnosis of RA. Nevertheless, about 15%–25% of RA patients are negative for both RA and ACPA, which can make RA diagnosis more difficult. Therefore, it is of great significance to find new autoantibodies or new biomarkers that can identify RF- and ACPA-negative patients for early diagnosis and prognosis of RA.
Adiponectin, a member of the adipokine group, is significantly increased in serum of RA patients. Studies have shown that adiponectin can be used as a biomarker to predict the degree of joint inflammation and bone erosion in RA patients. The complement component 1q tumor necrosis factor-related protein (CTRP) is highly homologous to adiponectin. It is also a class of adipokines and has a powerful biological function. The CTRP superfamily consists of 15 members from CTRP1 to CTRP15. CTRP proteins share a common structure: a signal peptide at the N terminus, a short variable region, a collagenous domain, and a C-terminal globular domain that is homologous to complement component 1q (C1q). At present, CTRPs are considered to have the dual functions of regulating metabolism and immunity, and are mostly studied in diabetes, obesity, cardiovascular and cerebrovascular diseases, fatty liver, immune-related diseases, and other diseases.
CTRP3 is the most intensively studied CTRP protein. Similar to adiponectin, CTRP3 is an adipokine that inhibits pro-inflammatory pathways. Several studies have found that CTRP3 could inhibit the production of Lipopolysaccharide (LPS)-induced inflammatory cytokines from human adipocytes, monocytes, and fibroblasts., Furthermore, it was found that CTRP3 could play a protective role in cartilage by regulating fibroblast growth factor receptor-1 signaling, which was considered a potential anti-osteoarthritis (OA) drug. At present, there is little research on CTPR 3 in RA. Until now, only Murayama et al. have found that CTRP3 plays a vital role in the development of collagen-induced arthritis in mice.
CTRP9 is a new adipocyte factor discovered in recent years, which plays an important role in regulating metabolism, protecting myocardium, improving endothelial function, inhibiting platelet (PLT) activation, and reducing the expression of inflammatory factors., CTRP9 has the highest homology with adiponectin, which can protect against inflammation-related diseases. About the study on OA, the results showed that CTRP9 can inhibit p38 mitogen-activated protein kinase and the nuclear factor-kappa B (NF-κB) signaling pathways to alleviate the inflammation of monosodium iodoacetate-induced OA rats. However, there is no research on CTRP9 and RA.
CTRP3 and CTRP9 have immunomodulatory effects. We suspect that they may also be closely related to RA. The main purpose of this study is to assess the expression of serum CTRP3 and CTRP9 in RA patients, and further explore their correlation with disease activity of RA and predictive value of RA.
| Methods|| |
The study was carried out on sixty RA patients (RA group) who were enrolled in the Center for Endocrine Metabolism and Immune Diseases, Beijing Luhe Hospital, Capital Medical University, during the period from March 2021 to August 2021. All RA patients were diagnosed according to the 2010 ACR/EULAR classification criteria for RA. Sixty healthy individuals (healthy group), who were matched for age and sex with the RA group, come from the physical examination center of Beijing Luhe Hospital, Capital Medical University. It is considered that some diseases are related to abnormal expression of CTRP3 and CTRP9, so all patients with the following conditions were excluded: pregnancy, infection, hypertension, diabetes, cardiovascular and cerebrovascular diseases, hyperlipidemia, other autoimmune diseases, as well as tumors. This study was approved by the Medical Ethics Committee of Beijing Luhe Hospital, Capital Medical University (Number 2021-LHKY-029). All participants gave informed consent to the study.
Clinical data collection
We collected and recorded the basic information (name, age, gender, disease duration, etc.) and laboratory parameters of all participants, including white blood cells (WBCs), PLTs, total cholesterol (TC), total triglyceride (TG), low-density lipoprotein (LDL), high-density lipoprotein (HDL), and uric acid (UA) in serum. In addition, RA patients also needed to collect inflammatory biomarkers, including erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), autoantibody antibodies (anti-CCP and RF), swollen joint counts (SJCs), tender joint counts (TJCs), and immunoglobulin (Ig) (IgA, IgM, and IgG).
We assessed the disease activity in RA patients by the Disease Activity Score using 28 joint counts (DAS28). The DAS28 was calculated by SJC28 (range: 0–28), TJC28 (range: 0–28), CRP (mg/L), as well as the Visual Analog Scale (range: 0–100) of RA patients.
Complement component 1q tumor necrosis factor-related protein 3 and complement component 1q tumor necrosis factor-related protein 9 in the serum were measured by enzyme-linked immunosorbent assay
At room temperature, we collected the 4 ml peripheral venous blood of all participants, which was placed for 30 min and centrifuged for 20 min (1,000 × g). The serum samples of the participants were removed and stored at −80°C. When we need to further analysis, the serum samples were thawed on ice. The level of serum CTRP3 and CTRP9 expression was measured by commercial enzyme-linked immunosorbent assay kits (Mlbio, Shanghai, China) in accordance with the manufacturer's instructions.
The data were analyzed using SPSS22.0 (IBM, Inc., Armonk, NY, USA) software. Quantitative data, including normal distribution variables and abnormal distribution variables, were respectively presented as mean ± standard deviation or median (P25, P75). Qualitative data were presented as number. The differences between the two groups were analyzed by the Student's t-test (two-tailed), nonparametric test (Mann–Whitney test), or Chi-square test. The correlation analysis was performed by Spearman correlation analysis. The predictive value of CTRP3 and CTRP9 in the serum was determined by constructing receiver operator characteristic (ROC) curve and calculating area under the curve (AUC). In addition, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of CTRP3 and CTRP9 as well as the combination of CTRP3 and CTRP9 were calculated. P < 0.05 was considered to be statistically significant.
| Results|| |
The expression of serum complement component 1q tumor necrosis factor-related protein 3 and complement component 1q tumor necrosis factor-related protein 9 in rheumatoid arthritis patients and healthy individuals
First of all, we explored the distribution of the basic information (age and gender) and laboratory parameters (WBC, PLT, TC, TG, etc.) between the RA group and the healthy group [Supplementary Table 1]. There was no significant difference in age and gender between the two groups (P > 0.05). However, compared with the healthy group, the expression of PLT (228.27 ± 62.27) (P < 0.05), TC (4.27 ± 0.91) (P < 0.001), LDL (2.62 ± 0.74) (P < 0.05), HDL (1.31 ± 0.40) (P < 0.05), and UA (255.85 ± 86.25) (P < 0.05) in the RA group was lower. In addition, we found that the expression of serum CTRP3 and CTRP9 in the RA group was higher than that in the healthy group [P < 0.05, [Table 1] and [Figure 1]].
|Figure 1: The expression of serum CTRP3 and CTRP9 in the RA group and the healthy group. (a) The expression of serum CTRP3; (b) The expression of serum CTRP9. CTRP: The complement C1q tumor necrosis factor-related protein. *P < 0.05; **P < 0.01. CTRP3: Complement component 1q tumor necrosis factor-related protein 3, CTRP9: Complement component 1q tumor necrosis factor-related protein 9, RA: Rheumatoid arthritis|
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|Table 1: The expression of component 1q tumor necrosis factor-related protein 3 and component 1q tumor necrosis factor-related protein 9 in serum|
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Correlation between the expression levels of complement component 1q tumor necrosis factor-related protein 3 and complement component 1q tumor necrosis factor-related protein 9 in serum and rheumatoid arthritis
We analyzed the correlation between the basic information of RA patients and the expression levels of CTRP3 and CTRP9 in serum. Age was positively correlated with the level of CTRP3 (r = 0.300, P = 0.021). Disease duration of RA has no correlation with the expression of CTRP3 and CTRP9. We further explored the predictive effect of CTRP3 and CTRP9 expression levels in serum on disease activity of RA. PLT, ESR, CRP, SJC, TJC, and DAS28 of RA patients were not related to the expression levels of CTRP3 and CTRP9. Additionally, IgA (r = 0.338, P = 0.010) was positively correlated with the level of serum CTRP9. RF (r = −0.310, P = 0.018) was negatively correlated with the expression of serum CTRP9. However, the level of anti-CCP antibody was unrelated to the expression of serum CTRP3 and CTRP9 [P > 0.05, [Table 2]].
|Table 2: Correlation between levels of component 1q tumor necrosis factor-related protein 3 and component 1q tumor necrosis factor-related protein 9 in serum and clinical and laboratory data in patients with rheumatoid arthritis|
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Predictive value of serum complement component 1q tumor necrosis factor-related protein 3 and complement component 1q tumor necrosis factor-related protein 9 for rheumatoid arthritis
ROC curve was used to show the accuracy of serum CTRP3 and CTRP9 in predicting RA. When the best cutoff value of serum CTRP3 was selected as 31.66 ng/ml, the AUC was 0.635 (P < 0.05), with 95% confidence interval (CI) (0.535–0.735), sensitivity of 60.3%, and specificity of 61.7%. When the best cutoff value was 34.39 ng/ml, serum CTRP9 for RA had higher specificity (95%), with the AUC (0.611, P < 0.05), 95% CI (0.51–0.713). In addition, combined serum CTRP3 and CTRP9 detection could greatly increase sensitivity (72.4%), NPV (70.2%), and accuracy (68.7%) to RA, with a higher AUC (0.706, P < 0.001, 95% CI: 0.613–0.9) [Figure 2] and [Table 3].
|Figure 2: ROC curve of serum CTRP3, CTRP9, and CTRP3 + CTRP9 for discrimination between the RA group and the healthy group. (a) Predictive value of detecting serum CTRP3 and CTRP9 separately in RA. (b) Predictive value of combined detection of serum CTRP3 and CTRP9 in RA. ROC: Receiver operator characteristic, CTRP3: Complement component 1q tumor necrosis factor-related protein 3, CTRP9: CTRP9: Complement component 1q tumor necrosis factor-related protein 9, RA: Rheumatoid arthritis|
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|Table 3: Predictive value of serum component 1q tumor necrosis factor-related protein 3 and component 1q tumor necrosis factor-related protein 9 for rheumatoid arthritis|
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| Discussion|| |
RA is a kind of autoimmune disease, featured with multi-joint bone destruction and multiple organs involved. People's low awareness, poor compliance, delayed diagnosis, improper treatment, and other reasons lead to a high disability and mortality rate of RA. The physical disability and serious complications often make the patients of RA suffer from physical and mental torture, which imposes a heavy burden on patients, families, and society. With the age-standardized prevalence and incidence rates increasing, RA has become a global public health challenge. Therefore, early diagnosis, finding effective treatment, and preventing and reducing complications have become the goal of rheumatologists. Finding candidate biomarkers are particularly important for diagnosing, judging disease activity, and predicting the prognosis of RA.
RF and ACPAs, including anti-CCP antibody, anti-MCV antibody, AKA, and APF, have been known in the diagnosis and prognosis of RA. However, ACPA and RF are not positive in all RA patients., Therefore, it is of great significance to find new candidate biomarkers for RA, especially for RA patients with negative RF and ACPA antibodies. In 2004, Wong et al. first introduced the term CTRPs, which were described as a new family of proteins homologous to adiponectin, composed of 15 members (CTRP1 to CTRP15). Studies have shown that CTRP3 and CTRP9 have anti-inflammatory, metabolic regulation, and cardiovascular protection effects.,,, At present, there is no research on CTRP3 and CTRP9 in patients with RA. We firstly explored the clinical significance of serum CTRP3 and CTRP9 expression in RA patients.
At the beginning of the study, compared with the healthy group, we found that the expression levels of TC, LDL, and HDL in RA patients were lower, which was consistent with the published results. It is known that TC, TG, LDL, and HDL can regulate the level of lipid metabolism. CTRP3 and CTRP9 are found to be closely related to TC, TG, LDL, and HDL in type 2 diabetes, cardiovascular disease and other diseases., However, in our study, we did not find that TC, TG, HDL, and LDL were related to the expression levels of serum CTRP3 and CTRP9. We suspected that it may be related to the exclusion of metabolic diseases, such as hyperlipidemia, diabetes, and cardiovascular and cerebrovascular diseases, or CTRP3 and CTRP9 were not involved in the lipid metabolism process of RA. Those aspects still need to be explored in the future.
According to difference in length and glycosylation, CTRP3, which is also called CORS-26, cartducin, and cartonectin, is divided into two subtypes: CTRP3A (40 kDa) and CTRP3B (32 kDa) in humans. Some studies have demonstrated that CTRP3, as a potential anti-inflammatory mediator, could stimulate endothelial cell proliferation and migration, could regulate inflammatory response, and is negatively correlated with pro-inflammatory cytokines, such as tumor necrosis factor, interleukin-6, and transforming growth factor-β.,, Meanwhile, some studies have found that serum CTRP3 is negatively correlated with osteoporosis and knee OA in postmenopausal women., CTRP3 can inhibit the activation of NF of activated T cells 1 (NFATc1) through AMP-activated protein kinase (AMPK) signaling pathway and play a negative regulatory role in receptor activator of NF-κB ligand-mediated osteoclast differentiation. Since synovitis and bone destruction exist in the pathogenesis of RA, the researchers hypothesize that CTRP3 might be associated with RA.
Murayama et al. first explored the pathogenic role of C1qtnf3, which encodes CTRP3, in collagen-induced arthritis. Compared with wild-type mice, the expression C1qtnf3 was higher in the joints of RA models and the joint severity and pro-inflammatory cytokine mRNAs were higher in C1qtnf3 (-/-) mice. Compared with the healthy group, we found that the level of serum CTRP3, like adiponectin, was higher in RA patients, suggesting that CTRP3 may be a candidate biomarker for RA.,, We suspected that CTRP3, like adiponectin, may have both anti-inflammatory and pro-inflammatory effects on RA patients. The mechanism will be further studied.
Interestingly, like adiponectin, we also found that age was positively correlated with the level of CTRP3. At present, it was considered that serum CTRP3 was closely related to Type 2 diabetes, obesity, cardiovascular diseases, etc. With the increase of age, the risk of these diseases also increases, which may be the reason for the age-related CTRP3. Meanwhile, in our studies, we did not find a correlation between serum CTRP3 expression and DAS28, ESR, CRP, SJC, and TJC, suggesting that serum CTRP3 may not be associated with RA disease activity. Similarly, adiponectin has previously been found not to be associated with RA disease activity. At present, there is little research on CTRP3 and RA, and whether CTRP3 participates in the pathogenesis of RA still needs further study.
CTRP9, another novel adipokine, is closest to adiponectin in CTRP family and has a similar metabolic regulation function with adiponectin. In addition to regulating metabolism, protecting myocardium and endothelium, CTRP9 also plays an important role in inhibiting the inflammatory response., Nevertheless, there are a few studies on CTRP9 in autoimmune diseases. Yang et al. findings suggest that CTRP9 may be a potential biomarker in SSc-associated interstitial lung disease. Interestingly, for the first time, we found that CTRP9 was highly expressed in serum of RA patients. Similar to our results, some studies also have found that the circulating levels of serum CTRP9 is upregulated in Type 2 diabetes mellitus and coronary artery disease. We hypothesized that the elevated CTRP9 levels may be a compensatory response to RA. The serum CTRP9 may be another candidate biomarker for RA. In the future, more studies are needed to confirm this. Moreover, the same as CTRP3, the expression of serum CTRP9 was not found to be related to disease activity in RA patients. To our surprise, our study also found a negative correlation between serum CTRP9 levels and RF. Similar results were obtained in the study of adiponectin in RA.
Up to now, no relevant research on the predictive value of serum CTRP3 and CTRP9 for RA has been reported. In this study, the sensitivity, specificity, PPV, NPV, and accuracy of CTRP3 and CTRP9 in RA patients were not ideal, which may be related to the insufficient sample size. However, we found that testing serum CTRP9 alone has high specificity for RA and combined detection of serum CTRP3 and CTRP9 could greatly improve the sensitivity, NPV, and accuracy of RA. These data suggested that the serum CTRP3 and CTRP9 may have certain predictive values for RA.
| Conclusion|| |
Our results demonstrate that CTRP3 and CTRP9 may become two candidate biomarkers for RA. The combined detection of serum CTRP3 and CTRP9 levels may be more significant in RA patients. However, the study of CTRP3 and CTRP9 in RA is still in its primary stage, and its mechanism is still unclear, which needs further study.
The data used to support the findings of this study are available from the corresponding author upon request.
Financial support and sponsorship
The work was supported by the Youth Scientific Research Incubation Program of Beijing Luhe Hospital, Capital Medical University in 2019 (Grant number: LHYY2019-LC05).
Conflicts of interest
There are no conflicts of interest.
| References|| |
Gonzalez A, Maradit Kremers H, Crowson CS, Nicola PJ, Davis JM 3rd
, Therneau TM, et al
. The widening mortality gap between rheumatoid arthritis patients and the general population. Arthritis Rheum 2007;56:3583-7.
Fazal SA, Khan M, Nishi SE, Alam F, Zarin N, Bari MT, et al
. A clinical update and global economic burden of rheumatoid arthritis. Endocr Metab Immune Disord Drug Targets 2018;18:98-109.
Aletaha D, Neogi T, Silman AJ, Funovits J, Felson DT, Bingham CO 3rd
, et al
. 2010 Rheumatoid arthritis classification criteria: An American College of Rheumatology/European League Against Rheumatism collaborative initiative. Arthritis Rheum 2010;62:2569-81.
Ingegnoli F, Castelli R, Gualtierotti R. Rheumatoid factors: C
linical applications. Dis Markers 2013;35:727-34.
Sun J, Zhang Y, Liu L, Liu G. Diagnostic accuracy of combined tests of Anti Cyclic citrullinated peptide antibody and rheumatoid factor for rheumatoid arthritis: A meta-analysis. Clin Exp Rheumatol 2014;32:11-21.
Haolong LI, Yongzhe LI. Research progress of biomarkers in rheumatoid arthritis. Chin J lab med 2019;42:723-30.
Khajoei S, Hassaninevisi M, Kianmehr N, Seif F, Khoshmirsafa M, Shekarabi M, et al
. Serum levels of adiponectin and vitamin D correlate with activity of rheumatoid arthritis. Mol Biol Rep 2019;46:2505-12.
Meyer M, Sellam J, Fellahi S, Kotti S, Bastard JP, Meyer O, et al
. Serum level of adiponectin is a surrogate independent biomarker of radiographic disease progression in early rheumatoid arthritis: Results from the ESPOIR cohort. Arthritis Res Ther 2013;15:R210.
Schäffler A, Buechler C. CTRP family: Linking immunity to metabolism. Trends Endocrinol Metab 2012;23:194-204.
Recinella L, Orlando G, Ferrante C, Chiavaroli A, Brunetti L, Leone S. Adipokines: New potential therapeutic target for obesity and metabolic, rheumatic, and cardiovascular diseases. Front Physiol 2020;11:578966.
Compton SA, Cheatham B. CTRP-3: Blocking a toll booth to obesity-related inflammation. Endocrinology 2010;151:5095-7.
Kopp A, Bala M, Buechler C, Falk W, Gross P, Neumeier M, et al
. C1q/TNF-related protein-3 represents a novel and endogenous lipopolysaccharide antagonist of the adipose tissue. Endocrinology 2010;151:5267-78.
Hofmann C, Chen N, Obermeier F, Paul G, Büchler C, Kopp A, et al
. C1q/TNF-related protein-3 (CTRP-3) is secreted by visceral adipose tissue and exerts antiinflammatory and antifibrotic effects in primary human colonic fibroblasts. Inflamm Bowel Dis 2011;17:2462-71.
Huang Y, Wan G, Tao J. C1q/TNF-related protein-3 exerts the chondroprotective effects in IL-1β-treated SW1353 cells by regulating the FGFR1 signaling. Biomed Pharmacother 2017;85:41-6.
Murayama MA, Kakuta S, Maruhashi T, Shimizu K, Seno A, Kubo S, et al
. CTRP3 plays an important role in the development of collagen-induced arthritis in mice. Biochem Biophys Res Commun 2014;443:42-8.
Yu XH, Zhang DW, Zheng XL, Tang CK. C1q tumor necrosis factor-related protein 9 in atherosclerosis: Mechanistic insights and therapeutic potential. Atherosclerosis 2018;276:109-16.
Yang Y, Li Y, Ma Z, Jiang S, Fan C, Hu W, et al
. A brief glimpse at CTRP3 and CTRP9 in lipid metabolism and cardiovascular protection. Prog Lipid Res 2016;64:170-7.
Zheng S, Ren J, Gong S, Qiao F, He J. CTRP9 protects against MIA-induced inflammation and knee cartilage damage by deactivating the MAPK/NF-κB pathway in rats with osteoarthritis. Open Life Sci 2020;15:971-80.
van Riel PL, Renskers L. The disease activity score (DAS) and the disease activity score using 28 joint counts (DAS28) in the management of rheumatoid arthritis. Clin Exp Rheumatol 2016;34:S40-4.
Safiri S, Kolahi AA, Hoy D, Smith E, Bettampadi D, Mansournia MA, et al
. Global, regional and national burden of rheumatoid arthritis 1990-2017: A systematic analysis of the Global Burden of Disease study 2017. Ann Rheum Dis 2019;78:1463-71.
Wu CY, Yang HY, Luo SF, Lai JH. From rheumatoid factor to anti-citrullinated protein antibodies and anti-carbamylated protein antibodies for diagnosis and prognosis prediction in patients with rheumatoid arthritis. Int J Mol Sci 2021;22:686.
Wong GW, Wang J, Hug C, Tsao TS, Lodish HF. A family of Acrp30/adiponectin structural and functional paralogs. Proc Natl Acad Sci USA 2004;101:10302-7.
Si Y, Fan W, Sun L. A review of the relationship between CTRP family and coronary artery disease. Curr Atheroscler Rep 2020;22:22.
Yan Z, Cao X, Wang C, Liu S, Li Y, Lu G, et al
. C1q/tumor necrosis factor-related protein-3 improves microvascular endothelial function in diabetes through the AMPK/eNOS/NO·signaling pathway. Biochem Pharmacol 2022;195:114745.
García-Chagollán M, Hernández-Martínez SE, Rojas-Romero AE, Muñoz-Valle JF, Sigala-Arellano R, Cerpa-Cruz S, et al
. Metabolic syndrome in rheumatoid arthritis patients: Relationship among its clinical components. J Clin Lab Anal 2021;35:e23666.
Seldin MM, Tan SY, Wong GW. Metabolic function of the CTRP family of hormones. Rev Endocr Metab Disord 2014;15:111-23.
Hwang YC, Woo Oh S, Park SW, Park CY. Association of serum C1q/TNF-related protein-9 (CTRP9) concentration with visceral adiposity and metabolic syndrome in humans. Int J Obes (Lond) 2014;38:1207-12.
Peterson JM, Wei Z, Wong GW. C1q/TNF-related protein-3 (CTRP3), a novel adipokine that regulates hepatic glucose output. J Biol Chem 2010;285:39691-701.
Akiyama H, Furukawa S, Wakisaka S, Maeda T. CTRP3/cartducin promotes proliferation and migration of endothelial cells. Mol Cell Biochem 2007;304:243-8.
Mohamadinarab M, Ahmadi R, Gholamrezayi A, Rahvar F, Naghdalipour M, Setayesh L, et al
. Serum levels of C1q/TNF-related protein-3 in inflammatory bowel disease patients and its inverse association with inflammatory cytokines and insulin resistance. IUBMB Life 2020;72:1698-704.
Jiang H, Wang M, Ye J, Liu J, Wang Z, Xu Y, et al.
Serum levels of complement-C1q/tumor necrosis factor-related protein-3 decreased in patients with acute aortic dissection. Am J Cardiol 2018;122:1244-8.
Xu ZH, Zhang X, Xie H, He J, Zhang WC, Jing DF, et al
. Serum CTRP3 level is associated with osteoporosis in postmenopausal women. Exp Clin Endocrinol Diabetes 2018;126:559-63.
Maghbooli Z, Hossein-Nezhad A, Khoshechin G, Niketeghad G, Moradi S, Adabi E, et al
. Possible association between circulating CTRP3 and knee osteoarthritis in postmenopausal women. Aging Clin Exp Res 2019;31:927-34.
Kim JY, Min JY, Baek JM, Ahn SJ, Jun HY, Yoon KH, et al
. CTRP3 acts as a negative regulator of osteoclastogenesis through AMPK-c-Fos-NFATc1 signaling in vitro
and RANKL-induced calvarial bone destruction in vivo
. Bone 2015;79:242-51.
Lee YH, Bae SC. Circulating adiponectin and visfatin levels in rheumatoid arthritis and their correlation with disease activity: A meta-analysis. Int J Rheum Dis 2018;21:664-72.
Szumilas K, Szumilas P, Słuczanowska-Głąbowska S, Zgutka K, Pawlik A. Role of adiponectin in the pathogenesis of rheumatoid arthritis. Int J Mol Sci 2020;21:8265.
Chen Q, Tian J, Wang J, Lu T, Zhou T, Zhou Q, et al
. Clinical significance of serum adiponectin on bone and joint damage in patients with rheumatoid arthritis. Clin Res Pract 2017;2:1-3.
Yang MM, Balmert LC, Marangoni RG, Carns M, Hinchcliff M, Korman BD, et al
. Circulating CTRP9 Is associated with severity of systemic sclerosis-associated interstitial lung disease. Arthritis Care Res (Hoboken) 2021:10.1002/acr.24749.
Zhou Y, Xu JH, Xu SQ, Zhang Y, Zhang MM. Changes and clinical significance of adiponectin in patients with rheumatoid arthritis. Chin J Rheumatol 2014;18:549-51.
[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3]