University of Oulu

Luukkonen, J., Huhtakangas, J., Palosaari, S., Tuukkanen, J., Vuolteenaho, O., & Lehenkari, P. (2022). Preliminary report: Osteoarthritis and rheumatoid arthritis synovial fluid increased osteoclastogenesis in vitro by monocyte differentiation pathway regulating cytokines. Mediators of Inflammation, 2022, 1–13.

Preliminary report : osteoarthritis and rheumatoid arthritis synovial fluid increased osteoclastogenesis In vitro by monocyte differentiation pathway regulating cytokines

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Author: Luukkonen, Jani1; Huhtakangas, Johanna1,2; Palosaari, Sanna1;
Organizations: 1Department of Anatomy and Cell Biology, Cancer Research and Translational Medicine Research Unit, Medical Research Center Oulu, Faculty of Medicine, University of Oulu, Aapistie 5, Oulu 90014, Finland
2Rheumatology Unit, Oulu University Hospital, Medical Research Center Oulu, Oulu, Finland
3Department of Clinical Chemistry, Cancer Research and Translational Medicine Research Unit, Faculty of Medicine, University of Oulu, Aapistie 5, 90014 Oulu, Finland
4NordLab Oulu, Kiviharjuntie 11, 90220 Oulu, Finland
5Department of Surgery, Medical Research Center Oulu, University of Oulu and University of Oulu Hospital, Finland
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 2.2 MB)
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Language: English
Published: Hindawi, 2022
Publish Date: 2023-03-08


Background: Rheumatoid arthritis (RA) and osteoarthritis (OA) are common joint diseases associated with changes in local, as well as systemic bone structure and osteoclast function. We investigated how the different soluble inflammatory stimuli in these diseases can affect osteoclastogenesis and bone resorption in vitro.

Methods: Human peripheral blood mononuclear cell-derived osteoclasts were cultured on bone slices with serum from treatment-naïve RA patients and healthy controls and with synovial fluid samples acquired from RA and OA patients. The concentrations of 29 different cytokines and related proteins, including RANKL and OPG, were analyzed in the fluids tested.

Results: RA serum and synovial fluid increased both osteoclastogenesis and bone resorption. Osteoclastogenesis and activity increased more in the cultures containing OA than RA synovial fluid. The osteoclasts cultured in different culture media exhibited different phenotypes, especially the cells cultured with OA synovial fluid were generally larger and had more nuclei. A general increase in proinflammatory cytokines in RA synovial fluid and serum was found. Surprisingly, OA synovial fluid showed lower levels of osteoclastogenesis inhibiting cytokines, such as IL-4 and IL-10, than RA synovial fluid, which at least partly explains more pronounced osteoclastogenesis. No significant difference was found in RANKL or OPG levels.

Conclusions: The proinflammatory stimulus in OA and RA drives the monocyte differentiation towards inflammatory osteoclastogenesis and altered osteoclast phenotype.

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Series: Mediators of inflammation
ISSN: 0962-9351
ISSN-E: 1466-1861
ISSN-L: 0962-9351
Volume: 2022
Article number: 2606916
DOI: 10.1155/2022/2606916
Type of Publication: A1 Journal article – refereed
Field of Science: 3111 Biomedicine
Funding: The authors would like to gratefully acknowledge Dr. Miho Nakamura and Prof. Yamashita Kimihiro of the Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, for allowing us to use their laser microscope in this study. MD Roni Pernu is thanked for helping to gather the healthy control serum samples. Medical statistician Mr. Pasi Ohtonen is acknowledged for statistical advice. This study was supported by Northern Ostrobothnia Hospital District Research Funding and Oulu University Hospital. JL was supported by Emil Aaltonen Foundation, JH was supported by The Finnish Medical Foundation, and SP was partly funded by Research Foundation for Rheumatic Diseases and Maire Lisko Foundation. Except for funding, the funding bodies did not have any other role in the design of the study or collection, analysis, and interpretation of data, or in writing the manuscript.
Copyright information: © 2022 Jani Luukkonen et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.