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FASEB journal : official publication of the Federation of American Societies for Experimental Biology2020; 34(3); 4430-4444; doi: 10.1096/fj.201902698R

Inflamed synovial fluid induces a homeostatic response in bone marrow mononuclear cells in vitro: Implications for joint therapy.

Abstract: Synovial inflammation is a central feature of osteoarthritis (OA), elicited when local regulatory macrophages (M2-like) become overwhelmed, activating an inflammatory response (M1-like). Bone marrow mononuclear cells (BMNC) are a source of naïve macrophages capable of reducing joint inflammation and producing molecules essential for cartilage metabolism. This study investigated the response of BMNC to normal (SF) and inflamed synovial fluid (ISF). Equine BMNC cultured in autologous SF or ISF (n = 8 horses) developed into macrophage-rich cultures with phenotypes similar to cells native to normal SF and became more confluent in ISF (~100%) than SF (~25%). BMNC cultured in SF or ISF were neither M1- nor M2-like, but exhibited aspects of both phenotypes and a regulatory immune response, characterized by increasing counts of IL-10 macrophages, decreasing IL-1β concentrations and progressively increasing IL-10 and IGF-1 concentrations. Changes were more marked in ISF and suggest that homeostatic mechanisms were preserved over time and were potentially favored by progressive cell proliferation. Collectively, our data suggest that intra-articular BMNC could increase synovial macrophage counts, potentiating the macrophage- and IL-10-associated mechanisms of joint homeostasis lost during the progression of OA, preserving the production of cytokines involved in tissue repair (PGE , IL-10) generally impaired by frequently used corticosteroids.
© 2020 Federation of American Societies for Experimental Biology.
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Publication Date: 2020-02-06 PubMed ID: 32030831DOI: 10.1096/fj.201902698RGoogle Scholar: Lookup
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The study investigates the in vitro response of bone marrow mononuclear cells (BMNC) to normal and inflamed synovial fluid and its implications for osteoarthritis treatment. It suggests that BMNC can boost joint homeostasis mechanisms lost to osteoarthritis progression and help preserve the production of tissue repair-related cytokines, offering a potential alternative to frequently used corticosteroids.

Research Study Breakdown

The study is a comprehensive exploration of bone marrow mononuclear cells and their response to normal and inflamed synovial fluid, primarily in the context of osteoarthritis. The bone marrow mononuclear cells are seen as a source of naïve macrophages which are capable of reducing joint inflammation and producing molecules essential for cartilage metabolism. The study is primarily focused on three areas:

  • The experimental setup: The study was carried out using bone marrow mononuclear cells from 8 horses, cultured in either autologous synovial fluid (SF) or inflamed synovial fluid (ISF). The equine BMNC developed into macrophage-rich cultures with phenotypes similar to cells native to normal SF. Interestingly, these cells became more confluent in ISF than in SF.
  • Cellular response: It was noticed that BMNC cultured in either SF or ISF exhibited both M1-like and M2-like phenotypes. This suggests that they have regulatory immune response characteristics. These include increasing counts of IL-10 macrophages, decreasing IL-1β concentrations, and progressively increasing IL-10 and IGF-1 concentrations. These changes were more marked in the cultures exposed to ISF, suggesting that homeostatic mechanisms were preserved over time and were potentially favored by progressive cell proliferation.
  • Implications for joint therapy: Based on the above findings, the researchers hypothesize that introducing BMNC into the joint (intra-articular) could potentially increase synovial macrophage counts. This process would in turn strengthen the joint’s homeostasis mechanisms that are usually impaired during the progression of osteoarthritis. Furthermore, it could preserve the production of cytokines involved in tissue repair, such as PGE and IL-10. These are typically impaired by frequently used corticosteroids in osteoarthritis treatment today.

The study hence suggests the potential of BMNC in providing a different perspective in osteoarthritis therapy, contrasting with the prevalent steroid-use based treatments.

Cite This Article

APA
Menarim BC, Gillis KH, Oliver A, Mason C, Werre SR, Luo X, Byron CR, Kalbfleisch TS, MacLeod JN, Dahlgren LA. (2020). Inflamed synovial fluid induces a homeostatic response in bone marrow mononuclear cells in vitro: Implications for joint therapy. FASEB J, 34(3), 4430-4444. https://doi.org/10.1096/fj.201902698R

Publication

FASEB journal : official publication of the Federation of American Societies for Experimental Biology
ISSN: 1530-6860
NlmUniqueID: 8804484
Country: United States
Language: English
Volume: 34
Issue: 3
Pages: 4430-4444

Researcher Affiliations

Menarim, Bruno C
  • Department of Large Animal Clinical Sciences, Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, VA, USA.
Gillis, Kiersten H
  • Department of Large Animal Clinical Sciences, Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, VA, USA.
Oliver, Andrea
  • Department of Large Animal Clinical Sciences, Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, VA, USA.
Mason, Caitlin
  • Department of Large Animal Clinical Sciences, Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, VA, USA.
Werre, Stephen R
  • Laboratory for Study Design and Statistical Analysis, Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, VA, USA.
Luo, Xin
  • Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, VA, USA.
Byron, Christopher R
  • Department of Large Animal Clinical Sciences, Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, VA, USA.
Kalbfleisch, Theodore S
  • Maxwell Gluck Equine Research Center, College of Agricultural and Veterinary Sciences, University of Kentucky, Lexington, KY, USA.
MacLeod, James N
  • Maxwell Gluck Equine Research Center, College of Agricultural and Veterinary Sciences, University of Kentucky, Lexington, KY, USA.
Dahlgren, Linda A
  • Department of Large Animal Clinical Sciences, Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, VA, USA.

MeSH Terms

  • Animals
  • Cell Proliferation / physiology
  • Cells, Cultured
  • Cytokines / metabolism
  • Female
  • Flow Cytometry
  • Horses
  • Insulin-Like Growth Factor I / metabolism
  • Interleukin-10 / metabolism
  • Interleukin-1beta / metabolism
  • Leukocytes, Mononuclear / metabolism
  • Macrophages / metabolism
  • Male
  • Synovial Fluid / metabolism
  • Synovitis / immunology
  • Synovitis / metabolism

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