1. Experimental arthritis was induced in rats by the intradermal injection of modified Freund's adjuvant. 2. The granulation tissue occurring in and around the joints was examined with the electron microscope. 3. Intracellular collagen was demonstrated in many of the cells. 4. Collagen formation by these cells was studied by autoradiographic techniques using tritiated proline as a label. 5. The proline turnover was rapid, as most of the labelled proline had become extracellular one hour after its injection. 6. It was concluded that the collagen was present within the cells as a result of phagocytosis despite the fact that the cells had the electron microscopic features of fibroblasts

Aims

Insufficient treatment response in rheumatoid arthritis (RA) patients requires novel treatment strategies to halt disease progression. The potential benefit of combination of cytokine-inhibitors in RA is still unclear and needs further investigation. To explore the impact of combined deficiency of two major cytokines, namely interleukin (IL)-1 and IL-6, in this study double deficient mice for IL-1αβ and IL-6 were investigated in different tumour necrosis factor (TNF)-driven inflammatory bone disorders, namely peripheral arthritis and sacroiliitis, as well as systemic bone loss.

Nerve growth factor (NGF) is involved in several joint diseases. It participates in pain initiation, inadequate nociception and neurogenic inflammation; its concentrations are increased in synovial fluid and tissue from human and experimental arthritis. However, data about its role in normal and pathological articular cartilage are scant and conflicting. This study assesses the effects of different. NGF concentrations on cultured healthy human chondrocytes by evaluating cell proliferation, cell phenotype, and gene expression. The 3-[4,5-dimethylthiazol-2-y1]-2,5-diphenyl-2H-tetrazolium bromide (MTT) test excluded an influence on cell viability; alcian blue and S100 staining demonstrated that NGF induced de-differentiation of the chondrocyte phenotype; real-time PCR disclosed that it reduced the expression of collagen type II (COL2A1) and transforming growth factor-β (TGF-β), key factors involved in articular cartilage integrity, and stimulated upregulation of metalloproteinase (MMP)-3 and MMP-13. These findings suggest that NGF may adversely affect differentiated chondrocytes from articular cartilage by inhibiting the expression of the collagens found in normal articular cartilage (COL2A1), while exerting a degradative effect though TGF-β downregulation and MMP-13 and MMP-3 upregulation. Further investigation is required to determine whether the gene expression pattern found in our study is associated with changes in protein expression

Aims

Osteoarthritis (OA) is a common degenerative joint disease characterized by chronic inflammatory articular cartilage degradation. Long noncoding RNAs (lncRNAs) have been previously indicated to play an important role in inflammation-related diseases. Herein, the current study set out to explore the involvement of lncRNA H19 in OA.

Rheumatoid arthritis (RA) is an autoimmune disease that involves T and B cells and their reciprocal immune interactions with proinflammatory cytokines. T cells, an essential part of the immune system, play an important role in RA. T helper 1 (Th1) cells induce interferon-γ (IFN-γ), tumour necrosis factor-α (TNF-α), and interleukin (IL)-2, which are proinflammatory cytokines, leading to cartilage destruction and bone erosion. Th2 cells primarily secrete IL-4, IL-5, and IL-13, which exert anti-inflammatory and anti-osteoclastogenic effects in inflammatory arthritis models. IL-22 secreted by Th17 cells promotes the proliferation of synovial fibroblasts through induction of the chemokine C-C chemokine ligand 2 (CCL2). T follicular helper (Tfh) cells produce IL-21, which is key for B cell stimulation by the C-X-C chemokine receptor 5 (CXCR5) and coexpression with programmed cell death-1 (PD-1) and/or inducible T cell costimulator (ICOS). PD-1 inhibits T cell proliferation and cytokine production. In addition, there are many immunomodulatory agents that promote or inhibit the immunomodulatory role of T helper cells in RA to alleviate disease progression. These findings help to elucidate the aetiology and treatment of RA and point us toward the next steps.

Cite this article: Bone Joint Res 2022;11(7):426–438.

Nitric oxide (NO) production by the inducible NO synthase (iNOS) and enhanced emigration of leukocytes into synovial tissue are suggested to play a crucial role in mediating chronic joint inflammation such as rheumatoid arthritis. The effects of iNOS inhibition in experimental arthritis are dicussed controversally. The aim of our study was to analyze the synovial microcirculation and leukocyte endothelial cell interactions in iNOS-deficient mice with antigen-induced arthritis (AiA) in vivo. 14 homocygote iNOS-deficient (iNOS KO C57BL6/J x 129SvEv; Merck & Co., Rahway, NJ, USA) and 14 iNOS-positive (C57BL6/J x 129SvEv) mice were used for our study. The patella tendon was resected, which allows for visualization of the intraarticular synovial tissue of the knee joint using intravital fluorescence microscopy. Animals were allocated into four groups (iNOS +/+, iNOS +/+ with AiA, iNOS −/− and iNOS −/− with AiA) (n=7 each group). On day 8 after arthritis induction, functional capillary density (FCD), fraction of rolling leukocytes, and the number of adherent leukocytes were quantitatively analyzed in synovial postcapillary venules. Histologic sections were performed to assess leukocyte infiltration of the synovium. FCD or leukocyte-endothelial cell interaction were not altered in healthy iNOS-deficient mice in comparison to iNOS +/+ animals. However, in iNOS-deficient animals with AiA there was a significant increase in the fraction of rolling (0,510,05) and in the number of adherent leukocytes (729126 mm-2) in comparison to wild type mice with AiA (0,330,07 and 565110 mm-2) (MWSEM, p < 0,05). Histologic sections revealed increased leukocyte infiltration in iNOS-deficient animals with AiA compared to iNOS +/+ arthritic animals. In our study, there was an enhanced leukocyte accumulation and extravasation in iNOS-deficient mice with antigen-induced arthritis in comparison to iNOS-positive animals with arthritis. Thus, the induction of iNOS appears as critical protective response to AiA possibly by reducing leukocyte adhesion and infiltration

Rheumatoid arthritis (RA) is an autoimmune disease characterized by symmetrical and chronic polyarthritis. Fibroblast-like synoviocytes are mainly involved in joint inflammation and cartilage and bone destruction by inflammatory cytokines and matrix-degrading enzymes in RA. Approaches that induce various cellular growth alterations of synoviocytes are considered as potential strategies for treating RA. However, since synoviocytes play a critical role in RA, the mechanism and hyperplastic modulation of synoviocytes and their motility need to be addressed. In this review, we focus on the alteration of synoviocyte signalling and cell fate provided by signalling proteins, various antioxidant molecules, enzymes, compounds, clinical candidates, to understand the pathology of the synoviocytes, and finally to achieve developed therapeutic strategies of RA.

Cite this article: Bone Joint Res 2021;10(4):285–297.

Aims

Rheumatoid arthritis (RA), which mainly results from fibroblast-like synoviocyte (FLS) dysfunction, is related to oxidative stress. Advanced oxidation protein products (AOPPs), which are proinflammatory mediators and a novel biomarker of oxidative stress, have been observed to accumulate significantly in the serum of RA patients. Here, we present the first investigation of the effects of AOPPs on RA-FLSs and the signalling pathway involved in AOPP-induced inflammatory responses and invasive behaviour.

The dynamic association between the immune system and the skeletal system has recently been appreciated. It has been suggested that cells involved in the inflammatory cascade might modulate the bone fracture repair process. Interestingly a number of studies have demonstrated that ability of the T lymphocyte to affect bone remodelling and health profoundly. For example the presence of T lymphocytes has been shown to increase bone resorption during experimental induced arthritis. We wanted to investigate the role of specific T lymphocytes in fracture repair and required an in vivo model to deplete CD4 and CD8 T lymphocytes selectively. Method The cell lines of Anti-L3T4 (CD4), Anti-Lyt-2 (CD8) and Anti-phytochrome were obtained from ECACC and produced by Edinburgh University group, Immunosolv. Anti-phytochrome (AFRC MAC 51) antibody was used as the control. To each group of 5 murine models 50ìL of CD4 or CD8 or control antibody was injected ip on days 0, 1, 2, 7, 8, and 9. The body weight and behaviour were measured. On day 20 the spleens were sampled and a single cell suspension was created for each murine model. PE CD8 antibody and FITC CD4 antibody were then added to each sample. Each spleen sample was then cell sorted using the FACS machine. Results Compared to the control group the murine model injected with CD4 antibody had only 1.14 % of CD4 T cells remaining (mean 2.462 % +/− 0.270). Similarly, the murine models injected with CD8 antibody had only 1.8% of CD8 T cells remaining (mean 1.723 % +/− 1.036). Conclusion Our results suggest that to investigate the role of T lymphocytes in fracture repair, specific T lymphocytes can be successfully depleted with the repeated use of antibodies

We evaluated the top 13 journals in trauma and orthopaedics by impact factor and looked at the longer-term effect regarding citations of their papers.

All 4951 papers published in these journals during 2007 and 2008 were reviewed and categorised by their type, subspecialty and super-specialty. All citations indexed through Google Scholar were reviewed to establish the rate of citation per paper at two, four and five years post-publication. The top five journals published a total of 1986 papers. Only three (0.15%) were on operative orthopaedic surgery and none were on trauma. Most (n = 1084, 54.5%) were about experimental basic science. Surgical papers had a lower rate of citation (2.18) at two years than basic science or clinical medical papers (4.68). However, by four years the rates were similar (26.57 for surgery, 30.35 for basic science/medical), which suggests that there is a considerable time lag before clinical surgical research has an impact.

We conclude that high impact journals do not address clinical research in surgery and when they do, there is a delay before such papers are cited. We suggest that a rate of citation at five years post-publication might be a more appropriate indicator of importance for papers in our specialty.

Cite this article: Bone Joint J 2014;96-B:414–19.

Chondral damage to the knee is common and, if left untreated, can proceed to degenerative osteoarthritis. In symptomatic patients established methods of management rely on the formation of fibrocartilage which has poor resistance to shear forces. The formation of hyaline or hyaline-like cartilage may be induced by implanting autologous, cultured chondrocytes into the chondral or osteochondral defect.

Autologous chondrocyte implantation may be used for full-thickness chondral or osteochondral injuries which are painful and debilitating with the aim of replacing damaged cartilage with hyaline or hyaline-like cartilage, leading to improved function. The intermediate and long-term functional and clinical results are promising.

We provide a review of autologous chondrocyte implantation and describe our experience with the technique at our institution with a mean follow-up of 32 months (1 to 9 years).

The procedure is shown to offer statistically significant improvement with advantages over other methods of management of chondral defects.