Pathophysiology of osteoarthritis

Rannou, François

doi:10.1007/978-1-910315-16-3_3

Cited by 4 publications

(5 citation statements)

References 56 publications

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“…6,15 Therefore, the resolution of inflammation is a needed event to interrupt the catabolic processes in OA and to reestablish a homeostatic synovial environment favorable for tissue anabolism and turnover. 16,17 In vitro, macrophages differentiate into a spectrum of phenotypes, with the extremes represented by cells displaying a classical pro-inflammatory (M1-like) or a suppressive/ healing (M2-like) response. These different activation states gave rise to the concept of macrophage activation or polarization.…”

Section: Introductionmentioning

confidence: 99%

“…Sustained joint damage impedes the resolution of the inflammatory response and related cytokines and catabolic enzymes lead to joint degeneration . Therefore, the resolution of inflammation is a needed event to interrupt the catabolic processes in OA and to reestablish a homeostatic synovial environment favorable for tissue anabolism and turnover …”

Section: Introductionmentioning

confidence: 99%

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

et al. 2020

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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.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

et al. 2020

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“…However, sustained joint damage impedes resolution of the inflammatory process, and cytokines and catabolic enzymes resulting from chronic inflammation adversely affect joint homeostasis, leading to degeneration (8, 21). Resolution of inflammation is required to interrupt the degenerative processes in OA and to provide an environment favorable for the repair of synovial tissues (22, 23).…”

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confidence: 99%

Autologous bone marrow mononuclear cells modulate joint homeostasis in an equinein vivomodel of synovitis

et al. 2019

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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.

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“…, IL-10 and IGF-1), impairing mechanisms of inflammation resolution and leading to chronic inflammation[ 45 , 47 ]. Ultimately, the perpetually increased production of cytokines and activation of catabolic enzymes causes further damage or aberrant remodeling of joint tissues[ 5 , 20 , 48 ].…”

Section: Synovial Macrophages – Fire Fighters In Synovial Inflammationmentioning

confidence: 99%

“…In summary, when the homeostatic functions of synovial macrophages become overwhelmed, they upregulate inflammation to ultimately recruit more macrophages and respond to the increased demands for repair[ 21 , 41 , 42 , 49 ]. Efficient resolution of inflammation is required to interrupt the catabolic processes in OA and to re-establish a homeostatic synovial environment[ 48 , 50 ] (Figure 1 ). Understanding the facts outlining the phenotypical response of synovial macrophages in both the initiation and resolution of joint inflammation is paramount for developing pro-resolving joint therapies[ 11 , 20 , 21 , 40 , 50 ].…”

Section: Synovial Macrophages – Fire Fighters In Synovial Inflammationmentioning

confidence: 99%

Bone marrow mononuclear cells for joint therapy: The role of macrophages in inflammation resolution and tissue repair

Menarim¹,

MacLeod²,

Dahlgren³

2021

WJSC

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Osteoarthritis (OA) is the most prevalent joint disease causing major disability and medical expenditures. Synovitis is a central feature of OA and is primarily driven by macrophages. Synovial macrophages not only drive inflammation but also its resolution, through a coordinated, simultaneous expression of pro- and anti-inflammatory mechanisms that are essential to counteract damage and recover homeostasis. Current OA therapies are largely based on anti-inflammatory principles and therefore block pro-inflammatory mechanisms such as prostaglandin E 2 and Nuclear factor-kappa B signaling pathways. However, such mechanisms are also innately required for mounting a pro-resolving response, and their blockage often results in chronic low-grade inflammation. Following minor injury, macrophages shield the damaged area and drive tissue repair. If the damage is more extensive, macrophages incite inflammation recruiting more macrophages from the bone marrow to maximize tissue repair and ultimately resolve inflammation. However, sustained damage and inflammation often overwhelms pro-resolving mechanisms of synovial macrophages leading to the chronic inflammation and related tissue degeneration observed in OA. Recently, experimental and clinical studies have shown that joint injection with autologous bone marrow mononuclear cells replenishes inflamed joints with macrophage and hematopoietic progenitors, enhancing mechanisms of inflammation resolution, providing remarkable and long-lasting effects. Besides creating an ideal environment for resolution with high concentrations of interleukin-10 and anabolic growth factors, macrophage progenitors also have a direct role in tissue repair. Macrophages constitute a large part of the early granulation tissue, and further transdifferentiate from myeloid into a mesenchymal phenotype. These cells, characterized as fibrocytes, are essential for repairing osteochondral defects. Ongoing “omics” studies focused on identifying key drivers of macrophage-mediated resolution of joint inflammation and those required for efficient osteochondral repair, have the potential to uncover ways for developing engineered macrophages or off-the-shelf pro-resolving therapies that can benefit patients suffering from many types of arthropaties, not only OA.

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Pathophysiology of osteoarthritis

Cited by 4 publications

References 56 publications

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

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

Autologous bone marrow mononuclear cells modulate joint homeostasis in an equinein vivomodel of synovitis

Bone marrow mononuclear cells for joint therapy: The role of macrophages in inflammation resolution and tissue repair

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