Appearance of calpain correlates with arthritis and cartilage destruction in collagen induced arthritic knee joints of mice.

Abstract Background: Rheumatoid arthritis (RA) is a chronic and systemic inflammatory disorder whose progression is modulated by fibroblast-like synoviocytes (FLSs). Cyclin-dependent kinase (CDK) inhibitor 1 (p21) regulates the activation of other CDKs, and we recently reported that p21 deficiency induces susceptibility to osteoarthritis. Here, we focused on joint inflammation to determine the mechanisms associated with p21 function in synovial and cartilage tissues in RA.Methods: p21-knockout (p21-/-) mice and wild-type C57BL/6 (WT p21+/+) mice were used to establish a collagen antibody-induced arthritis (CAIA) model. The severity of arthritis was evaluated visually, and histological and immunohistological analyses performed 7, 14, and 28 days after injection with a cocktail of five monoclonal antibodies that recognize conserved epitopes on various species of type II collagen. The response of p21 siRNA-treated human RA FLSs to IL-1β stimulation was also determined.Results: Arthritis scores were higher in p21-/- mice than those in p21+/+ mice. More severe and prolonged synovitis of the knee joints and earlier loss of staining and cartilage destruction were observed in p21-/- mice than in p21+/+ mice. p21-/- mice expressed higher levels of IL-1β, F4/80, p-IKKα/β, and MMPs in cartilage and synovial tissues at each time point, except for before injection of the monoclonal antibodies, via IL-1β-induced NF-kB signaling. IL-1β stimulation significantly increased MMP expression and enhanced IKKα/β phosphorylation in human FLSs.Conclusion: p21-deficient CAIA mice are susceptible to alterations in the RA phenotype, including joint cartilage destruction and severe synovitis, via IL-1β-induced inflammation. Therefore, p21 regulation may constitute a possible strategy for RA treatment.

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Intra-articular Injection of Chitosan-Based Supramolecular Hydrogel for Osteoarthritis Treatment

Tissue Engineering and Regenerative Medicine ◽

10.1007/s13770-020-00322-z ◽

2021 ◽

Vol 18 (1) ◽

pp. 113-125

Author(s):

Donggang Mou ◽

Qunying Yu ◽

Jimei Zhang ◽

Jianping Zhou ◽

Xinmin Li ◽

...

Keyword(s):

Hyaluronic Acid ◽

Cartilage Destruction ◽

Knee Joints ◽

Self Healing ◽

Supramolecular Hydrogel ◽

Tnf Α ◽

Osteoarthritis Treatment ◽

Good Biocompatibility ◽

In Situ Crosslinking ◽

And Cartilage

Abstract Background: Pain and cartilage destruction caused by osteoarthritis (OA) is a major challenge in clinical treatment. Traditional intra-articular injection of hyaluronic acid (HA) can relieve the disease, but limited by the difficulty of long-term maintenance of efficacy. Methods: In this study, an injectable and self-healing hydrogel was synthesized by in situ crosslinking of N-carboxyethyl chitosan (N-chitosan), adipic acid dihydrazide (ADH), and hyaluronic acid–aldehyde (HA-ALD). Results: This supramolecular hydrogel sustains good biocompatibility for chondrocytes. Intra-articular injection of this novel hydrogel can significantly alleviate the local inflammation microenvironment in knee joints, through inhibiting the inflammatory cytokines (such as TNF-α, IL-1β, IL-6 and IL-17) in the synovial fluid and cartilage at 2- and even 12-weeks post-injection. Histological and behavioral test indicated that hydrogel injection protected cartilage destruction and relieved pain in OA rats, in comparison to HA injection. Conclusion: This kind of novel hydrogel, which is superior to the traditional HA injection, reveals a great potential for the treatment of OA.

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Managing Osteoporosis and Joint Damage in Patients with Rheumatoid Arthritis: An Overview

Journal of Clinical Medicine ◽

10.3390/jcm10061241 ◽

2021 ◽

Vol 10 (6) ◽

pp. 1241

Author(s):

Yoshiya Tanaka

Keyword(s):

Rheumatoid Arthritis ◽

Structural Damage ◽

Kinase Inhibitors ◽

Joint Destruction ◽

Joint Damage ◽

Nuclear Factor Κb ◽

Cartilage Destruction ◽

Janus Kinase ◽

Systemic Autoimmune Disease ◽

And Cartilage

In rheumatoid arthritis, a representative systemic autoimmune disease, immune abnormality and accompanying persistent synovitis cause bone and cartilage destruction and systemic osteoporosis. Biologics targeting tumor necrosis factor, which plays a central role in the inflammatory process, and Janus kinase inhibitors have been introduced in the treatment of rheumatoid arthritis, making clinical remission a realistic treatment goal. These drugs can prevent structural damage to bone and cartilage. In addition, osteoporosis, caused by factors such as menopause, aging, immobility, and glucocorticoid use, can be treated with bisphosphonates and the anti-receptor activator of the nuclear factor-κB ligand antibody. An imbalance in the immune system in rheumatoid arthritis induces an imbalance in bone metabolism. However, osteoporosis and bone and cartilage destruction occur through totally different mechanisms. Understanding the mechanisms underlying osteoporosis and joint destruction in rheumatoid arthritis leads to improved care and the development of new treatments.

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Prostaglandins and Rheumatoid Arthritis

Arthritis ◽

10.1155/2012/239310 ◽

2012 ◽

Vol 2012 ◽

pp. 1-7 ◽

Cited By ~ 37

Author(s):

Mohammad Javad Fattahi ◽

Abbas Mirshafiey

Keyword(s):

Rheumatoid Arthritis ◽

Arachidonic Acid ◽

Immune Responses ◽

Cartilage Destruction ◽

Heterogeneous Population ◽

Therapeutic Protocol ◽

Site Of Action ◽

And Cartilage ◽

Homeostatic Mechanisms

Rheumatoid arthritis (RA) is a chronic, autoimmune, and complex inflammatory disease leading to bone and cartilage destruction, whose cause remains obscure. Accumulation of genetic susceptibility, environmental factors, and dysregulated immune responses are necessary for mounting this self-reacting disease. Inflamed joints are infiltrated by a heterogeneous population of cellular and soluble mediators of the immune system, such as T cells, B cells, macrophages, cytokines, and prostaglandins (PGs). Prostaglandins are lipid inflammatory mediators derived from the arachidonic acid by multienzymatic reactions. They both sustain homeostatic mechanisms and mediate pathogenic processes, including the inflammatory reaction. They play both beneficial and harmful roles during inflammation, according to their site of action and the etiology of the inflammatory response. With respect to the role of PGs in inflammation, they can be effective mediators in the pathophysiology of RA. Thus the use of agonists or antagonists of PG receptors may be considered as a new therapeutic protocol in RA. In this paper, we try to elucidate the role of PGs in the immunopathology of RA.

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