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Inflamed synovial fluid induces a homeostatic response in bone marrow mononuclear cells in vitro: Implications for joint therapy
Author(s) -
Menarim Bruno C.,
Gillis Kiersten H.,
Oliver Andrea,
Mason Caitlin,
Werre Stephen R.,
Luo Xin,
Byron Christopher R.,
Kalbfleisch Theodore S.,
MacLeod James N.,
Dahlgren Linda A.
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.201902698r
Subject(s) - peripheral blood mononuclear cell , synovial fluid , bone marrow , homeostasis , in vitro , medicine , microbiology and biotechnology , immunology , pathology , chemistry , biology , osteoarthritis , biochemistry , alternative medicine
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 2 , IL‐10) generally impaired by frequently used corticosteroids.