Main Article Content


Background: An inflammatory condition that affects the joints in the limbs is rheumatoid arthritis. The most common symptom is chronic, recurrent joint inflammation. When patients are advanced, joint deformities and impairments may cause major impediments in the cardiac, skin, as well as other tissues and organs. A protein called cellular CCN3 is implicated in many biological processes such as cell adhesion, migration, as well as proliferation. Additionally, CCN3 has a role in a number of pathological processes, such as fibrosis, angiogenesis, and wound healing. CCN3 can be released from the cytoplasm. CCN3 may also be an inflammatory component in the course of RA. Future therapy approaches that focus on the activities and mechanisms of action of these proteins may result from better knowledge of how CCN proteins alter the pathophysiological processes underlying these types of arthritis and successfully reduce patients' pain (Wei et al., 2020). It was discovered that RA sera and tissues had increased levels of all CCN family members. IL6 production and CCN3 expression are correlated with disease activity (Giusti & Scotlandi, 2021).

Methods: Between November 2021 and April 2022, a study including 70 patients with RA who met four or more 2010 American College of Rheumatology and European League Against Rheumatism (ACR/EULAR) classification criteria for the condition and 70 healthy persons serving as control groups was conducted. All subjects had their disease activity score (DAS28-ESR), clinical activity index (CDAI), and rheumatoid factors (RF) detected by latex agglutination. By using an enzyme-linked immunosorbent assay, the levels of anti-cyclic citrullinated peptide (ACCP) and CCN3 in human serum samples were determined (ELISA).The age group of both the patients and the controls included in this study was 20-70. RA was found to be high in individuals of the age group >40 years, at a percentage of 71.4%. The mean age was 46.2±10.3 years for patients and 1.7±0.5 for controls.Results:  The results clearly showed high serum CCN3 levels in patient groups with RA compared to control (P = 0.0001). CCN3 and ACCP have a significantly positive association  at control (P = 0.0001). According to DAS28-ESR, there were significantly increased concentrations of  CCN3 in severe patients at  P values of  0.0001 in comparison to mild patients.

Conclusions: The biomarker CCN3 is a good prognostic marker for the severity of RA.



Rheumatoid arthritis; Cellular Communication Network factor 3; Rheumatoid factor; Anti-cyclic citrullinated peptide

Article Details

How to Cite
Saleem Zayed, N. ., Fadhil Obaid , R., & Ameer Hamza , . D. A. . (2022). Association Of Cellular Communication Network Factor 3 (CCN3) With Rheumatoid Arthritis Disease And It’s Severity (Case-Control Study). Medical Science Journal for Advance Research, 3(4), 201–208.


  1. • Catrina , A.I, et al. (2016). Mechanisms involved in triggering rheumatoid arthritis. 162–174.
  2. • Chammas, R., Mondragón Martínez, L., Coccaro, N., Liao, X., Jia, Q., Xu, B., Zhang, Y., & Ali, A. (2021). CCN Family Proteins in Cancer: Insight Into Their Structures and Coordination Role in Tumor Microenvironment. Front. Genet, 12, 649387.
  3. • Conforti, A., Di Cola, I., Pavlych, V., Ruscitti, P., Berardicurti, O., Ursini, F., Giacomelli, R., & Cipriani, P. (2021). Beyond the joints, the extra-articular manifestations in rheumatoid arthritis. Autoimmunity Reviews, 20(2), 102735.
  4. • Figus, F. A., Piga, M., Azzolin, I., McConnell, R., & Iagnocco, A. (2021). Rheumatoid arthritis: Extra-articular manifestations and comorbidities. Autoimmunity Reviews, 20(4).
  5. • Gautam, S., Kumar, U., & Dada, R. (2021). Yoga and its impact on chronic inflammatory autoimmune arthritis. Frontiers in Bioscience - Elite, 26(1).
  6. • Huang, X., Ni, B., Mao, Z., Xi, Y., Chu, X., Zhang, R., Ma, X., & You, H. (2019). NOV/CCN3 induces cartilage protection by inhibiting PI3K/AKT/mTOR pathway. Journal of Cellular and Molecular Medicine, 23(11), 7525–7534.
  7. • Janune, D., Abd El Kader, T., Aoyama, E., Nishida, T., Tabata, Y., Kubota, S., & Takigawa, M. (2017). Novel role of CCN3 that maintains the differentiated phenotype of articular cartilage. Journal of Bone and Mineral Metabolism, 35(6), 582–597.
  8. • Kubota, S., Kawaki, H., Perbal, B., Kawata, K., Hattori, T., & Nishida, T. (2021). Cellular communication network factor 3 in cartilage development and maintenance. Journal of Cell Communication and Signaling, 15(4), 533–543.
  9. • Li, J. Y., Wang, Y. Di, Qi, X. Y., Ran, L., Hong, T., Yang, J., Yan, B., Liao, Z. Z., Liu, J. H., & Xiao, X. H. (2019). Serum CCN3 levels are increased in type 2 diabetes mellitus and associated with obesity, insulin resistance and inflammation. Clinica Chimica Acta, 494(March), 52–57.
  10. • MacDonald, I. J., Huang, C.-C., Liu, S.-C., Lin, Y.-Y., & Tang, C.-H. (2021). Molecular Sciences Targeting CCN Proteins in Rheumatoid Arthritis and Osteoarthritis.
  11. • Maiuolo, J., Muscoli, C., Gliozzi, M., Musolino, V., Carresi, C., Paone, S., Ilari, S., Mollace, R., Palma, E., & Mollace, V. (2021). Endothelial dysfunction and extra-articular neurological manifestations in rheumatoid arthritis. Biomolecules, 11(1), 1–18.
  12. • Nogueira, E., Gomes, A., Preto, A., & Cavaco-Paulo, A. (2016). Update on Therapeutic Approaches for Rheumatoid Arthritis. Current Medicinal Chemistry, 23(21), 2190–2203.
  13. • Pakradouni, J., Goff, L., Calmel, W., Antoine, C., & Villard, B. (2013). Plasma NOV/CCN3 Levels Are Closely Associated with Obesity in Patients with Metabolic Disorders) Plasma NOV/CCN3 Levels Are Closely Associated with Obesity in Patients with Metabolic. Disorders. PLoS ONE, 8(6), 66788.
  14. • Peng, L., Wei, Y., Shao, Y., Li, Y., Liu, N., & Duan, L. (2021a). The Emerging Roles of CCN3 Protein in Immune-Related Diseases.
  15. • Peng, L., Wei, Y., Shao, Y., Li, Y., Liu, N., & Duan, L. (2021). The Emerging Roles of CCN3 Protein in Immune-Related Diseases. Mediators of Inflammation, 2021.
  16. • Saklani Kala, J., Agari, R., Kumar Singh, A., & Professor, A. (2021). a Review Article on Amavata W.S.R. Rheumatoid Arthritis. 08(04), 734–744.
  17. • Stoel, B. (2020). Use of artificial intelligence in imaging in rheumatology-current status and future perspectives. RMD Open, 6(1), 1–10.
  18. • Taylor, P. C., Moore, • Adam, Vasilescu, R., Alvir, J., & Tarallo, M. (2016). A structured literature review of the burden of illness and unmet needs in patients with rheumatoid arthritis: a current perspective. Rheumatology International, 36.
  19. • Wang, H., Huang, B., Hou, A., Xue, L., Wang, B., Chen, J., Li, M., & Zhang, J. V. (2021). High NOV/CCN3 expression during high-fat diet pregnancy in mice affects GLUT3 expression and the mTOR pathway. American Journal of Physiology - Heart and Circulatory Physiology, 320(4), E786–E796.