About this Research Topic
Rheumatic and osteoarticular diseases (including Osteoarthritis, Rheumatoid Arthritis, Osteoporosis) represent the most diffuse chronic conditions in the elderly, which affect the individual’s working abilities and autonomy, as well as life expectancy. These chronic inflammatory diseases share similar pathophysiological pathways including increased bone remodeling/resorption, a senescence-associated phenotype, and accumulation of activated immune cells and soluble factors in the joints and skeletal tissue.
Osteoarthritis (OA): Metabolic-triggered inflammation involving cytokines, adipokines, abnormal metabolites, acute phase reactants, and even complement, all appear to play major roles in the pathophysiology of OA. Immune-mediated inflammation involving T and B cells as well as macrophages is now considered a common finding in OA synovial tissue. The pro-inflammatory cytokines which stimulate MMP (matrix metalloproteinase) and ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) gene transcription in normal and OA human chondrocyte cultures are also significantly increased in the synovial fluid of OA patients. MMP and ADAMTS are involved in joint cartilage degradation and are associated with the severity of cartilage and subchondral bone damage.
Rheumatoid Arthritis (RA): Synovial inflammation is considered as pathognomonic of RA, despite RA is a systemic disease and a variety of immunological events occur outside the joint. Two key pathogenetic changes in the synovium are evident in RA. Firstly, the intimal lining greatly expands owing to an increase and activation of both macrophage-like and fibroblast-like synoviocytes (FLS), which are a prominent source of pro-inflammatory cytokines (such as IL-1, IL-6, and TNF) and of proteases (MMP) and small-molecule mediators (prostaglandins and leukotrienes), respectively. Secondly, adaptive immune cells infiltrate into the synovial sublining. CD4+ memory T cells can either diffusely infiltrate the tissue or form ectopic germinal centres in which mature B cells proliferate, differentiate and produce antibodies. Antigen-presenting follicular dendritic cells, macrophages and mast cells are also distributed through the synovial sublining.
Osteoporosis is an inflammatory condition characterized by the systemic impairment of bone mass microarchitecture. This condition is a major cause of fragility fractures and associated morbidity in the aged population. Osteoporosis results from a preponderant activity of osteoclasts over that of osteoblasts. Activated T cells are major stimulators of osteoclastogenesis. They produce the so-called bone-resorbing cytokines, especially RANKL (receptor activator of nuclear factor-κB ligand) and TNF-α. In addition, IL-1 and IL-6 are also among the ‘classic’ bone-resorbing proinflammatory cytokines. Overall, the activation of osteoclasts via these cytokines leads to exaggerated systemic, and in some diseases such as RA also local, bone loss. IL-17 is a further example of a proinflammatory cytokine that – by upregulation of RANKL – promotes bone resorption.
Despite the awareness of the importance of inflammatory dysregulation, the increasing knowledge that joint tissues contribute to damage in various osteoarticular diseases and that the disease progression can develop over a long period of time, many questions remain unanswered. Moreover, it is not surprising that treatments, either pharmacological or surgical, only partially address the clinical issue. Therefore, a more in-depth understanding of the mechanisms underlying the development of these disorders could lead to earlier intervention and to the identification of alternative, more appropriate, and less invasive therapeutic approaches.
This Research Topic calls for Original Research articles, Reviews, Mini-Reviews, and Perspectives that address the progress and current knowledge on the immunobiological characteristics and pathophysiological mechanisms of osteoarticular disease development. Potential topics include, but are not limited to:
1) Immunological mechanisms regulating inflammation in osteoarticular diseases.
2) Role of different immune populations and/or soluble factors in the development, diagnosis, and progression of osteoarticular diseases.
3) Relationship between inflammation and metabolism (such as in the Metabolic Syndrome dysregulation).
4) How the gut immune axis influences osteoarticular inflammatory responses.
5) Role of immunogenetics in predisposition to osteoarticular diseases.
6) Novel strategies to develop personalized therapies for osteoarticular diseases.
Osteoarthritis (OA): Metabolic-triggered inflammation involving cytokines, adipokines, abnormal metabolites, acute phase reactants, and even complement, all appear to play major roles in the pathophysiology of OA. Immune-mediated inflammation involving T and B cells as well as macrophages is now considered a common finding in OA synovial tissue. The pro-inflammatory cytokines which stimulate MMP (matrix metalloproteinase) and ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) gene transcription in normal and OA human chondrocyte cultures are also significantly increased in the synovial fluid of OA patients. MMP and ADAMTS are involved in joint cartilage degradation and are associated with the severity of cartilage and subchondral bone damage.
Rheumatoid Arthritis (RA): Synovial inflammation is considered as pathognomonic of RA, despite RA is a systemic disease and a variety of immunological events occur outside the joint. Two key pathogenetic changes in the synovium are evident in RA. Firstly, the intimal lining greatly expands owing to an increase and activation of both macrophage-like and fibroblast-like synoviocytes (FLS), which are a prominent source of pro-inflammatory cytokines (such as IL-1, IL-6, and TNF) and of proteases (MMP) and small-molecule mediators (prostaglandins and leukotrienes), respectively. Secondly, adaptive immune cells infiltrate into the synovial sublining. CD4+ memory T cells can either diffusely infiltrate the tissue or form ectopic germinal centres in which mature B cells proliferate, differentiate and produce antibodies. Antigen-presenting follicular dendritic cells, macrophages and mast cells are also distributed through the synovial sublining.
Osteoporosis is an inflammatory condition characterized by the systemic impairment of bone mass microarchitecture. This condition is a major cause of fragility fractures and associated morbidity in the aged population. Osteoporosis results from a preponderant activity of osteoclasts over that of osteoblasts. Activated T cells are major stimulators of osteoclastogenesis. They produce the so-called bone-resorbing cytokines, especially RANKL (receptor activator of nuclear factor-κB ligand) and TNF-α. In addition, IL-1 and IL-6 are also among the ‘classic’ bone-resorbing proinflammatory cytokines. Overall, the activation of osteoclasts via these cytokines leads to exaggerated systemic, and in some diseases such as RA also local, bone loss. IL-17 is a further example of a proinflammatory cytokine that – by upregulation of RANKL – promotes bone resorption.
Despite the awareness of the importance of inflammatory dysregulation, the increasing knowledge that joint tissues contribute to damage in various osteoarticular diseases and that the disease progression can develop over a long period of time, many questions remain unanswered. Moreover, it is not surprising that treatments, either pharmacological or surgical, only partially address the clinical issue. Therefore, a more in-depth understanding of the mechanisms underlying the development of these disorders could lead to earlier intervention and to the identification of alternative, more appropriate, and less invasive therapeutic approaches.
This Research Topic calls for Original Research articles, Reviews, Mini-Reviews, and Perspectives that address the progress and current knowledge on the immunobiological characteristics and pathophysiological mechanisms of osteoarticular disease development. Potential topics include, but are not limited to:
1) Immunological mechanisms regulating inflammation in osteoarticular diseases.
2) Role of different immune populations and/or soluble factors in the development, diagnosis, and progression of osteoarticular diseases.
3) Relationship between inflammation and metabolism (such as in the Metabolic Syndrome dysregulation).
4) How the gut immune axis influences osteoarticular inflammatory responses.
5) Role of immunogenetics in predisposition to osteoarticular diseases.
6) Novel strategies to develop personalized therapies for osteoarticular diseases.
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