CD14+ monocytes and soluble CD14 of synovial fluid are associated with osteoarthritis progression

Ha-Reum Lee; Sunyoung Lee; In Seol Yoo; Su-Jin Yoo; Mi-Hye Kwon; Chung-Il Joung; Ji Ah Park; Seong Wook Kang; Jinhyun Kim

doi:10.46497/ArchRheumatol.2022.9078

CD14+ monocytes and soluble CD14 of synovial fluid are associated with osteoarthritis progression

Arch Rheumatol. 2022 Mar 3;37(3):335-343. doi: 10.46497/ArchRheumatol.2022.9078. eCollection 2022 Sep.

Authors

Ha-Reum Lee^{1

2}, Sunyoung Lee¹, In Seol Yoo¹, Su-Jin Yoo¹, Mi-Hye Kwon³, Chung-Il Joung³, Ji Ah Park¹, Seong Wook Kang^{1

2}, Jinhyun Kim¹

Affiliations

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

Abstract

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.

Keywords: Cytokines; monocytes; osteoarthritis; synovial fluid..