Role of Innate Immunity in Initiation and Progression of Osteoarthritis, with Emphasis on Horses

McDermott, Juan Estrada; Pezzanite, Lynn M.; Goodrich, Laurie R.; Santangelo, Kelly S.; Chow, Lyndah; Dow, Steven; Wheat, William H.

doi:10.3390/ani11113247

Cited by 14 publications

(11 citation statements)

References 99 publications

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“…While an imbalance between cartilage degradation and new matrix synthesis leading to cartilage damage is considered central to the pathogenesis of OA, the involvement of an inflammatory component has now been well-recognized. Recent literature suggests that an innate immune response mediated by the joint components such as synovial membrane, joint capsule, subchondral bone and ligaments is responsible for initiating and sustaining an immune-mediated inflammation in the diseased joint ( 38 – 41 ). It is important to recognize that early inflammation, in response to joint injury is beneficial for the repair process.…”

Section: Principles Of Gene Therapymentioning

confidence: 99%

Gene therapy approaches for equine osteoarthritis

Thampi

Samulski²,

Grieger³

et al. 2022

Front. Vet. Sci.

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With an intrinsically low ability for self-repair, articular cartilage injuries often progress to cartilage loss and joint degeneration resulting in osteoarthritis (OA). Osteoarthritis and the associated articular cartilage changes can be debilitating, resulting in lameness and functional disability both in human and equine patients. While articular cartilage damage plays a central role in the pathogenesis of OA, the contribution of other joint tissues to the pathogenesis of OA has increasingly been recognized thus prompting a whole organ approach for therapeutic strategies. Gene therapy methods have generated significant interest in OA therapy in recent years. These utilize viral or non-viral vectors to deliver therapeutic molecules directly into the joint space with the goal of reprogramming the cells' machinery to secrete high levels of the target protein at the site of injection. Several viral vector-based approaches have demonstrated successful gene transfer with persistent therapeutic levels of transgene expression in the equine joint. As an experimental model, horses represent the pathology of human OA more accurately compared to other animal models. The anatomical and biomechanical similarities between equine and human joints also allow for the use of similar imaging and diagnostic methods as used in humans. In addition, horses experience naturally occurring OA and undergo similar therapies as human patients and, therefore, are a clinically relevant patient population. Thus, further studies utilizing this equine model would not only help advance the field of human OA therapy but also benefit the clinical equine patients with naturally occurring joint disease. In this review, we discuss the advancements in gene therapeutic approaches for the treatment of OA with the horse as a relevant patient population as well as an effective and commonly utilized species as a translational model.

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Section: Principles Of Gene Therapymentioning

confidence: 99%

Gene therapy approaches for equine osteoarthritis

Thampi

Samulski²,

Grieger³

et al. 2022

Front. Vet. Sci.

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“…In this study, we first reported a significant increase in TGF-β1 and VEGF in ACS of the OA dogs compared to the sham plasma control, similar to the previous report in human OA [ 16 ]. These growth factors are believed to play a role in joint homeostasis [ 25 ] and vascular regeneration [ 8 , 38 ], which are essential for joint and tendon repairs [ 36 , 39 ]. However, previous reports investigating ACS in normal dogs did not find the differences in these cytokines when compared to the normal serum [ 15 , 20 ].…”

Section: Discussionmentioning

confidence: 99%

“…Using autologous bioactive agents enriched in anti-inflammatory mediators and growth factors for tissue regeneration has become a novel insight for OA management [ 11 , 23 ]. Apart from the IL-1 receptor modulation, several recent studies suggest that T cell-mediated response plays a significant role in the aggravation of OA, including an increase in activated T cells in synovial fluid and synovial membrane [ 24 , 25 ]. As a result, the immune mediated degeneration of the joint prevents the healing process.…”

Section: Introductionmentioning

confidence: 99%

In Vitro Anti-Inflammatory and Regenerative Effects of Autologous Conditioned Serum from Dogs with Osteoarthritis

Soontararak

Ardaum

Senarat

et al. 2022

Animals

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Osteoarthritis (OA) is mostly incurable and non-regenerative with long-term complications. Autologous conditioned serum (ACS), which is enriched in Interleukin 1 receptor antagonists (IL-1RA) and growth factors, could be an alternative treatment to accelerate the positive therapeutic effects. ACS is proposed to alleviate inflammation by blocking IL-1 receptors. However, to date, there is no report focusing on the cell-mediated anti-inflammation and regenerative effect caused by ACS, especially the ACS from patients. Therefore, this study aims to investigate the therapeutic potential of ACS generated from dogs with spontaneous OA, focusing on its promising anti-inflammatory and regenerative properties in vitro compared to the matched plasma. We found that ACS prepared from ten OA dogs contained significant concentrations of IL-1RA, vascular endothelial growth factor, and transforming growth factor beta, which are key cytokines in anti-inflammation and angiogenesis. Furthermore, we found that ACS suppressed T cell activity by reducing proliferation of effector T cells and simultaneously expanding numbers of immune suppressive FOXP3+ T cells. Lastly, we showed that ACS enhanced the proliferation of osteocytes and fibroblasts and promoted extracellular matrix gene expression in primary chondrocyte culture. Therefore, these studies indicate that ACS prepared from dogs with OA is active as an immunomodulatory and regenerative strategy for use in OA management.

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“…Synovial fluid in a healthy joint contains no or few immune cells. The synovium is the most critical joint structure in its ability to mount an inflammatory response [25]. Neutrophils are the most common immune cell found in inflamed joint synovial fluid.…”

Section: Trafficking Of Circulating Blood Neutrophils To the Synovial...mentioning

confidence: 99%

The Importance of Neutrophils in Osteoarthritis: Current Concepts and Therapeutic Perspectives

Mehrani

Junqani

Morovati

et al. 2023

Immuno

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Osteoarthritis (OA) is the most common degenerative joint disease that causes chronic pain and disability. Different innate immune components, including macrophages, T cells, and neutrophils, participate in OA pathophysiology. Neutrophils are the most abundant circulating leukocytes with multiple specialized functions contributing to innate and adaptive immune functions. Although neutrophils produce proinflammatory cytokines and chemokines, reactive oxygen species (ROS), matrix-degrading enzymes, and neutrophil extracellular traps (NET) that promote joint degradation as the first recruit cells in an inflamed joint, these cells also play an important role in joint repair by regulating the immune response, releasing anti-inflammatory factors, and activating certain protective genes. In this review, various aspects of neutrophil biology, their role in inflammation and its association with OA, and possible therapeutic approaches to target neutrophils for the treatment of OA are described. Since neutrophils play a complex role in the pathophysiology of osteoarthritis, contributing to joint degradation as well as joint repair, targeting these cells is likely to pave the way for a potential therapeutic approach for the management of OA. Future studies are needed to investigate the use of targeted therapies to modulate neutrophil function and identify their subpopulations that are associated with osteoarthritis progression or response to treatment.

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Role of Innate Immunity in Initiation and Progression of Osteoarthritis, with Emphasis on Horses

Cited by 14 publications

References 99 publications

Gene therapy approaches for equine osteoarthritis

Gene therapy approaches for equine osteoarthritis

In Vitro Anti-Inflammatory and Regenerative Effects of Autologous Conditioned Serum from Dogs with Osteoarthritis

The Importance of Neutrophils in Osteoarthritis: Current Concepts and Therapeutic Perspectives

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