Tenascin-C is an endogenous activator of Toll-like receptor 4 that is essential for maintaining inflammation in arthritic joint disease

Osteoarthritis is a progressive joint disease characterized by degeneration and destruction of articular cartilage. The incidence of osteoarthritis has increased steadily over the years leading to more than 50% in people over the age of 65. Due to associated side effects of prevailing therapeutics, better drugs are needed for osteoarthritis management. Asiaticoside is a bioactive component isolated from the medicinal plant Centella asiatica. It has been reported to possess neuroprotective, antiulcer, wound healing, anti-inflammatory, antioxidative, and other pharmacological properties. However, the potential of asiaticoside in the management of osteoarthritis remains to be explored. To this end, we examined the effect of asiaticoside on lipopolysaccharides induced inflammatory injury and apoptosis of chondrocytes. The results show that asiaticoside promotes viability and decrease in apoptosis of ATDC5 cells through decreased production of proinflammatory cytokines and the regulation of toll-like receptor 4/nuclear factor-kappa b signaling pathway. In summary, our results provide the evidence that asiaticoside could serve as a promising therapeutic drug for osteoarthritis treatment.

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Tenascin‑C promotes the migration of bone marrow stem cells via toll‑like receptor 4‑mediated signaling pathways: MAPK, AKT and Wnt

Molecular Medicine Reports ◽

10.3892/mmr.2018.8855 ◽

2018 ◽

Author(s):

Huaiyu Ding ◽

Mingyu Jin ◽

Dai Liu ◽

Shujing Wang ◽

Jianing Zhang ◽

...

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Signaling Pathways ◽

Bone Marrow Stem Cells ◽

Toll Like Receptor ◽

Toll Like Receptor 4 ◽

Tenascin C

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Did Tenascin-C Co-Evolve With the General Immune System of Vertebrates?

Frontiers in Immunology ◽

10.3389/fimmu.2021.663902 ◽

2021 ◽

Vol 12 ◽

Author(s):

Gertraud Orend ◽

Richard P. Tucker

Keyword(s):

Extracellular Matrix ◽

Adaptive Immunity ◽

Lymphoid Tissues ◽

Toll Like Receptor ◽

Toll Like Receptor 4 ◽

Tenascin C ◽

Histocompatibility Complex ◽

Reticular Fibers ◽

Regulatory Functions ◽

Lymphocyte Receptors

Tenascin-C plays important roles in immunity. Toll-like receptor 4, integrin α9β1 and chemokines have already been identified as key players in executing the immune regulatory functions of tenascin-C. Tenascin-C is also found in reticular fibers in lymphoid tissues, which are major sites involved in the regulation of adaptive immunity. Did the “tool box” for reading and interpreting the immune-regulating instructions imposed by tenascins and tenascin-C co-evolve? Though the extracellular matrix is ancient, tenascins evolved relatively recently. Tenascin-like genes are first encountered in cephalochordates and urochordates, which are widely accepted as the early branching chordate lineages. Vertebrates lacking jaws like the lamprey have tenascins, but a tenascin gene that clusters in the tenascin-C clade first appears in cartilaginous fish. Adaptive immunity apparently evolved independently in jawless and jawed vertebrates, with the former using variable lymphocyte receptors for antigen recognition, and the latter using immunoglobulins. Thus, while tenascins predate the appearance of adaptive immunity, the first tenascin-C appears to have evolved in the first organisms with immunoglobulin-based adaptive immunity. While a C-X-C chemokine is present in the lamprey, C-C chemokines also appear in the first organisms with immunoglobulin-based adaptive immunity, as does the major histocompatibility complex, T-cell receptors, Toll-like receptor 4 and integrin α9β1. Given the importance of tenascin-C in inflammatory events, the co-evolution of tenascin-C and key elements of adaptive and innate immunity is suggestive of a fundamental role for this extracellular matrix glycoprotein in the immune response of jawed vertebrates.

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Tenascin-C Levels, A Toll-like Receptor 4 Ligand, in Enthesitis-related Arthritis Category of Juvenile Idiopathic Arthritis: A Cross-sectional and Longitudinal Study

The Journal of Rheumatology ◽

10.3899/jrheum.141365 ◽

2015 ◽

Vol 42 (5) ◽

pp. 891-896 ◽

Cited By ~ 5

Author(s):

Anuj Shukla ◽

Priyanka Gaur ◽

Amita Aggarwal

Keyword(s):

Disease Activity ◽

Nsaid Therapy ◽

Inactive Disease ◽

Toll Like Receptor ◽

Characteristic Analysis ◽

Toll Like Receptor 4 ◽

Enthesitis Related Arthritis ◽

Tenascin C ◽

Control Serum ◽

Paired Serum

Objective.Monocytes of children with enthesitis-related arthritis (ERA) show Toll-like receptor 4 (TLR4) overexpression. Tenascin-C (TNC) is an extracellular matrix glycoprotein and acts as an endogenous TLR4 ligand. Thus, we studied the serum and synovial fluid (SF) levels of TNC in children with ERA.Methods.TNC was measured in the serum of 80 children with ERA satisfying the International League of Associations for Rheumatology criteria. Fifteen children were followed up while being treated with regular nonsteroidal antiinflammatory drug (NSAID) therapy and levels were reassessed at 3 months. Seventeen paired serum-SF samples and 25 healthy control serum samples were also analyzed. Disease activity was assessed by physician’s global assessment (PGA), early morning stiffness (EMS), tender (TJC) and swollen joint counts (SJC), enthesitis score, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP).Results.The mean serum TNC level in patients with active disease (67.1 ± 44.9 ng/ml) was significantly higher than in those with inactive disease (40.6 ± 36.7 ng/ml, p = 0.01) and healthy controls (21 ± 15.2 ng/ml, p < 0.001). Levels of TNC were higher in HLA-B27–positive (58.4 ng/ml) versus −negative disease (20.4 ng/ml, p = 0.01). TNC levels correlated moderately with disease activity: PGA r = 0.4, EMS r = 0.34, TJC r = 0.4, SJC r = 0.46, ESR r = 0.42, and CRP r = 0.32. In receiver-operation characteristic analysis for active versus inactive diseases, TNC [area under the curve (AUC) = 0.754] was equivalent to ESR (AUC = 0.787) and CRP (AUC = 0.789). Regular NSAID therapy led to a significant fall in serum TNC levels at 3 months (p = 0.0003). The SF TNC level was 17.39 ng/ml, significantly lower than the paired serum values (p = 0.01).Conclusion.Serum TNC levels are significantly raised and correlate with various clinical and laboratory variables of disease activity in children with ERA. Regular NSAID therapy reduces the TNC levels, probably related to controlling disease activity.

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