Ha-Reum Lee1,2, Sunyoung Lee1, In Seol Yoo1, Su-Jin Yoo1 , Mi-Hye Kwon3, Chung-il Joung3, Ji Ah Park1, Seong Wook Kang1,2, Jinhyun Kim1

1Department of Internal Medicine, Division of Rheumatology, Chungnam National University Hospital, Daejeon, Republic of Korea
2Research Institute for Medical Sciences, Chungnam National University School of Medicine, Daejeon, Republic of Korea
3Department of Internal Medicine, Konyang University School of Medicine, Daejeon, Republic of Korea

Keywords: Cytokines, monocytes, osteoarthritis, synovial fluid.


Objectives: This study aims to investigate the role of cluster of differentiation 14 (CD14) expressed monocytes and soluble CD14-mediated pathway in the synovial inflammation of knee osteoarthritis (OA).

Patients and methods: Between May 2012 and July 2013, a total of 35 patients with knee OA (9 males, 26 females; mean age: 66.3±8.8 years; range, 52 to 79 years) were included in this cross-sectional study. Synovial fluid was obtained from knee joints of 35 OA patients. The CD14+ monocytes from synovial fluid mononuclear cells (SFMCs) were isolated using the MACS. The fibroblast-like synoviocytes (FLSs) isolated from knee joint tissue were incubated with recombinant CD14 and lipopolysaccharide (LPS) for 24 h. Cytokine profiling was performed with the Luminex® Performance Assay or magnetic bead panel kit. The expression of CD14 and CD16 was analyzed by immunohistochemistry and flow cytometry.

Results: The concentration of sCD14 in synovial fluid was correlated with the interleukin-6 (IL-6) level (n=35) (ρ=0.654, p<0.001). The culture supernatants of CD14+ monocytes isolated from SFMC (n=15) showed a correlation between sCD14 and IL-6 (ρ=0.784, p=0.001), along with complement component 3 (ρ=0.756, p=0.010), IL-1b (ρ=0.652, p=0.012), and tumor necrosis factor-alpha (ρ=0.806, p=0.001). Following recombinant CD14 and LPS treatment, OA FLS synergistically enhanced the secretion of IL-6, IL-8, and matrix metalloproteinase 3 (n=3, p<0.05). In five paired-samples from identical patients, the proportions of CD14+ monocytes were significantly elevated in recurred synovial fluid compared to those in initial synovial fluid (p=0.043). When monocyte subsets were analyzed in SFMC (n=26), CD14+CD16+monocytes were abundant (p=0.019) and had higher toll-like receptor 4 expression than CD14+CD16- (p<0.001).

Conclusion: Our study results suggest that CD14+ monocytes and the sCD14-mediated pathway play an important role in OA aggravation through inflammatory cytokine secretion.

Citation: Lee HR, Lee S, Yoo IS, Yoo SJ, Kwon MH, Joung CI, et al. CD14+ monocytes and soluble CD14 of synovial fluid are associated with osteoarthritis progression. Arch Rheumatol 2022;37(3):335-343.

Ethics Committee Approval

The study protocol was approved by the Chungnam National University Hospital Institutional Review Board (2012-04-008 and 2018-05-061). The study was conducted in accordance with the principles of the Declaration of Helsinki.

Author Contributions

Validation and visualization, project administration and writing: H.R.L.; Data curation, investigation, resources, validation and visualization: S.L.; Data curation, investigation, and resources: I.S.Y., S.J.Y., M.H.K., C.I.J., J.A.P.; Conceptualization and methodology: S.W.K.; Conceptualization and methodology, project administration, writing and supervision: J.K.

Conflict of Interest

The authors declared no conflicts of interest with respect to the authorship and/or publication of this article.

Financial Disclosure

This work was supported by the Chungnam National University Hospital Research Fund 2013.