Osteoarthritis (OA) is characterized by macrophage-driven synovitis. Macrophages promote synovial health but become inflammatory when their regulatory functions are overwhelmed. Bone marrow mononuclear cells (BMNCs) are a rich source of macrophage progenitors used for treating chronic inflammation and produce essential molecules for cartilage metabolism. This study investigated the response to autologous BMNC injection in normal and inflamed joints. Synovitis was induced in both radiocarpal joints of 6 horses. After 8 h, 1 inflamed radiocarpal and 1 normal tarsocrural joint received BMNC injection. Contralateral joints were injected with saline. Synovial fluid was collected at 24, 96, and 144 h for cytology, cytokine quantification, and flow cytometry. At 144 h, horses were euthanatized, joints were evaluated, and synovium was harvested for histology and immunohistochemistry. Four days after BMNC treatment, inflamed joints had 24% higher macrophage counts with 10% more IL-10 + cells than saline-treated controls. BMNC-treated joints showed gross and analytical improvements in synovial fluid and synovial membrane, with increasing regulatory macrophages and synovial fluid IL-10 concentrations compared with saline-treated controls. BMNC-treated joints were comparable to healthy joints histologically, which remained abnormal in saline-treated controls. Autologous BMNCs are readily available, regulate synovitis through macrophage-associated effects, and can benefit thousands of patients with OA.

No 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 (PGE2, IL‐10) generally impaired by frequently used corticosteroids.