Abstract Low-grade inflammation is part of the pathogenesis of osteoarthritis (OA) from its earliest stages and contributes to the acceleration of the degenerative process. Innate immunity has a leading role in it. Activation of the innate immune response is initiated by stimulation of the receptors on the cell membrane to recognize the secreted PAMPs (pathogen-associated molecular patterns). However, PAMPs can also be activated by endogenous damage-related molecular patterns (DAMPs). The group of DAMPs also includes toll-like receptors (TLRs).The disruption of matrix homeostasis in the course of OA is an example of activation of these receptors in chronic damage. The complement system is a key element of the innate immune system. It is one of the serum enzyme systems whose function is to opsonize antigens. The complement receptors on the surface of the cell membranes adhere to the targets for phagocytosis. The C3R fraction activates the complement cascade itself, as well as the oxygen metabolism of the cell, which is essential for the phagocytosis. The cartilage damage products released during joint damage are a separate class of potent complement modulators. Complement fractions bind to complement receptors on the surface of the chondrocyte and the synoviocyte cell membranes by TLR. The complement system is involved in many processes in the course of osteoarthritis: chondrocyte degeneration, ECM degradation, low-grade inflammation in the osteoarthritis, cell lysis, unbalanced bone remodeling, osteophyte formation, and neoangiogenesis. Whether drug control of complement activation may be a future therapeutic strategy in the treatment of OA and prevent its progression is a subject of future studies.
Osteoimmunology (OI) is a relatively new field in medicine, improving our understanding of the pathogenesis of the rheumatic diseases. OI focuses on the relationship and interaction between the immune and the musculoskeletal systems, observing these processes in three main aspects: regulating the bone resorption by the immune system, the impact of inflammation on the bone formation, the role of bone and bone marrow as a depot for immune cells. Changes in the bone architecture may be due to the activation of the immune system. Proinflammatory cytokines leading in the pathogenesis ofthe inflammatory joint disease are potent activators of nuclear factor-kB receptor activator (RANKL) expression and thus promote the osteoclast differentiation. This link explains why therapy whose target are the cytokines , especially TNF inhibition, is very effective in delaying structural damage in rheumatic diseases. Knowledge of these mechanisms would allow better use of medical therapies to reduce skeletal damage.
The bone and immune cells all share the same microenvironment, interact with each other, share common signaling pathways, collaborate, performing the functions of an "osteoimmune system". The same cytokines may have different and often opposite effects depending on the specific environment in which they function, the maturation stage of the target cells and/or the influence of other cytokines. Through osteoimmunology, the intimate mechanisms in the pathogenesis of many rheumatological diseases such as Rheumatoid arthritis, axSpA, autoinflammatory diseases, osteonecrosis, osteoarthrosis, osteoporosis are clarified. Osteoimmunology is a conceptual framework for decoding the complex language through which the immune system and bone communicate. This review summarizes the data accumulated to date on the interactions between the immune and bone systems of the human organism and reveals the bidirectionality of these interactions and their role in the pathogenesis of rheumatic joint and bone diseases.
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