Cytokines and Chemokines Involved in Osteoarthritis Pathogenesis

Molnar, Vilim; Matišić, Vid; Kodvanj, Ivan; Bjelica, Roko; Jeleč, Željko; Hudetz, Damir; Rod, Eduard; Čukelj, Fabijan; Vrdoljak, Trpimir; Vidović, Dinko; Silva, Mario; Sabalić, Srećko; Dobričić, Borut; Petrović, Tadija; Antičević, Darko; Borić, Igor; Košir, Rok; Zmrzljak, Uršula Prosenc; Primorac, Dragan

doi:10.3390/ijms22179208

Cited by 276 publications

(218 citation statements)

References 187 publications

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“…E. B. Yannai and colleagues investigated the antioxidant capacity of CA and N-acetyl CA compounds in microglial oxidative stress and inflammation-induced in brain cells caused by lipopolysaccharide (LPS) [ 98 ]. In the fight against infections, inflammation is a necessary cellular response [ 5 ]. Chronic and uncontrolled inflammation is linked to the pathophysiology of many human diseases, including autoimmune diseases, neurological disorders, diabetes, and bone-related diseases [ 99 ].…”

Section: Discussionmentioning

confidence: 99%

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Carnosine Alleviates Knee Osteoarthritis and Promotes Synoviocyte Protection via Activating the Nrf2/HO-1 Signaling Pathway: An In-Vivo and In-Vitro Study

et al. 2022

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The most common joint disease in the elderly is knee osteoarthritis (OA). It is distinguished by cartilage degradation, subchondral bone loss, and a decrease in joint space. We studied the effects of carnosine (CA) on knee OA in male Wistar rats. OA is induced by anterior cruciate ligament transection combined with medial meniscectomy (ACLT+MMx) method and in vitro studies are conducted in fibroblast-like synoviocyte cells (FLS). The pain was assessed using weight-bearing and paw-withdrawal tests. CA supplementation significantly reduced pain. The enzyme-linked immunosorbent assay (ELISA) method was used to detect inflammatory proteins in the blood and intra-articular synovial fluid (IASF), and CA reduced the levels of inflammatory proteins. Histopathological studies were performed on knee-tissue samples using toluidine blue and hematoxylin and eosin (H and E) assays. CA treatment improved synovial protection and decreased cartilage degradation while decreasing zonal depth lesions. Furthermore, Western blotting studies revealed that the CA-treated group activated nuclear factor erythroid 2-related factor (Nrf2) and heme oxygenase (HO-1) and reduced the expression of cyclooxygenase-2 (COX-2). FLS cells were isolated from the knee joints and treated with IL-1β to stimulate the inflammatory response and increase reactive oxygen species (ROS). The matrix metalloproteinase protein (MMP’s) levels (MMP-3, and MMP-13) were determined using the reverse transcription-polymerase chain reaction (RT-PCR), and CA treatment reduced the MMP’s expression levels. When tested using the 2′,7′-dicholorodihydrofluroscene diacetate (DCFDA) assay and the 5,5′,6,6′-tetracholoro-1,1′,3,3′-tertraethylbenzimidazolcarboc janine iodide (JC-1) assay in augmented ROS FLS cells, CA reduced the ROS levels and improved the mitochondrial membrane permeability. This study’s investigation suggests that CA significantly alleviates knee OA both in vitro and in vivo.

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Section: Discussionmentioning

confidence: 99%

“…AC absorbs movement-induced stress and provides a smooth platform for efficient joint motions. AC is composed of type II collagen and aggrecans proteoglycans, which work together to increase bone strength and flexibility [ 5 , 6 ].…”

Section: Introductionmentioning

confidence: 99%

Carnosine Alleviates Knee Osteoarthritis and Promotes Synoviocyte Protection via Activating the Nrf2/HO-1 Signaling Pathway: An In-Vivo and In-Vitro Study

et al. 2022

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“…Both BM-MSCs and AD-MSCs secrete anti-inflammatory cytokine IL-10 [ 169 , 178 , 179 ]. IL-10 has an anti-inflammatory effect by downregulating catabolic matrix metalloproteinase (MMP) production [ 130 ].…”

Section: Mechanism Of Actionmentioning

confidence: 99%

“…MSC-derived IL-10 induces regulatory DC differentiation as well [ 183 ]. Other anti-inflammatory properties of IL-10 are stimulation of macrophages to synthesize IL-1β antagonists, as well as inhibition of TNF-α, IL-6, and IL-12 [ 178 ]. IL-10 and HLA-G5 are linked in an amplification feedback loop, mutually increasing their concentrations and anti-inflammatory effect [ 176 ].…”

Section: Mechanism Of Actionmentioning

confidence: 99%

Mesenchymal Stem Cell Mechanisms of Action and Clinical Effects in Osteoarthritis: A Narrative Review

Molnar

Pavelić²,

Vrdoljak

et al. 2022

Genes

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With the insufficient satisfaction rates and high cost of operative treatment for osteoarthritis (OA), alternatives have been sought. Furthermore, the inability of current medications to arrest disease progression has led to rapidly growing clinical research relating to mesenchymal stem cells (MSCs). The availability and function of MSCs vary according to tissue source. The three primary sources include the placenta, bone marrow, and adipose tissue, all of which offer excellent safety profiles. The primary mechanisms of action are trophic and immunomodulatory effects, which prevent the further degradation of joints. However, the function and degree to which benefits are observed vary significantly based on the exosomes secreted by MSCs. Paracrine and autocrine mechanisms prevent cell apoptosis and tissue fibrosis, initiate angiogenesis, and stimulate mitosis via growth factors. MSCs have even been shown to exhibit antimicrobial effects. Clinical results incorporating clinical scores and objective radiological imaging have been promising, but a lack of standardization in isolating MSCs prevents their incorporation in current guidelines.

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“…IL-1β levels have been shown to have a positive correlation with OA changes ( Daheshia and Yao, 2008 ; Denoble et al, 2011 ). Similarly, the pro-inflammatory chemokine IL-8 (or CXCL8) is high in the synovium of OA patients ( Kaneko et al, 2000 ; Pierzchala et al, 2011 ; Molnar et al, 2021 ) and its level is linked to clinical severity ( García-Manrique et al, 2021 ). IL-10 is also present in the osteoarthritic joint, but is considered an anti-inflammatory cytokine ( Iannone et al, 2001 ) known to inhibit inflammatory arthritis progression in mice ( Choi et al, 2008 ).…”

Section: Introductionmentioning

confidence: 99%

In vitro Exposure to Inflammatory Mediators Affects the Differentiation of Mesenchymal Progenitors

Marsh

Constantin-Teodosiu

Chapman

et al. 2022

Front. Bioeng. Biotechnol.

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The increasing prevalence of joint disease, and in particular osteoarthritis (OA), calls for novel treatment strategies to prevent disease progression in addition to existing approaches focusing mainly on the relief of pain symptoms. The inherent properties of mesenchymal stem cells (MSCs) make them an attractive candidate for novel tissue repair strategies, as these progenitors have the potential to differentiate into chondrocytes needed to replace degraded cartilage and can exert a modulating effect on the inflammatory environment of the diseased joint. However, the inflammatory environment of the joint may affect the ability of these cells to functionally integrate into the host tissue and exert beneficial effects, as hinted by a lack of success seen in clinical trials. Identification of factors and cell signalling pathways that influence MSC function is therefore critical for ensuring their success in the clinic, and here the effects of inflammatory mediators on bone marrow-derived MSCs were evaluated. Human MSCs were cultured in the presence of inflammatory mediators typically associated with OA pathology (IL-1β, IL-8, IL-10). While exposure to these factors did not produce marked effects on MSC proliferation, changes were observed when the mediators were added under differentiating conditions. Results collected over 21 days showed that exposure to IL-1β significantly affected the differentiation response of these cells exposed to chondrogenic and osteogenic conditions, with gene expression analysis indicating changes in MAPK, Wnt and TLR signalling pathways, alongside an increased expression of pro-inflammatory cytokines and cartilage degrading enzymes. These results highlight the value of MSCs as a preclinical model to study OA and provide a basis to define the impact of factors driving OA pathology on the therapeutic potential of MSCs for novel OA treatments.

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Cytokines and Chemokines Involved in Osteoarthritis Pathogenesis

Cited by 276 publications

References 187 publications

Carnosine Alleviates Knee Osteoarthritis and Promotes Synoviocyte Protection via Activating the Nrf2/HO-1 Signaling Pathway: An In-Vivo and In-Vitro Study

Carnosine Alleviates Knee Osteoarthritis and Promotes Synoviocyte Protection via Activating the Nrf2/HO-1 Signaling Pathway: An In-Vivo and In-Vitro Study

Mesenchymal Stem Cell Mechanisms of Action and Clinical Effects in Osteoarthritis: A Narrative Review

In vitro Exposure to Inflammatory Mediators Affects the Differentiation of Mesenchymal Progenitors

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