Characterization of degenerative human facet joints and facet joint capsular tissues.

OBJECTIVE: Lumbar facet joint degeneration (FJD) may be an important cause of low back pain (LBP) and sciatica. The goal of this study was to characterize cellular alterations of inflammatory factor expression and neovascularization in human degenerative facet joint capsular (FJC) tissue. These alterations in FJC tissues in pain stimulation were also assessed. DESIGN: FJs were obtained from consented patients undergoing spinal reconstruction surgery and cadaveric donors with no history of back pain. Histological analyses of the FJs were performed. Cytokine antibody array and quantitative real-time polymerase chain reaction (qPCR) were used to determine the production of inflammatory cytokines, and western blotting analyses (WB) were used to assay for cartilage-degrading enzymes and pain mediators. Ex vivo rat dorsal root ganglion (DRG) co-culture with human FJC tissues was also performed. RESULTS: Increased neovascularization, inflammatory cell infiltration, and pain-related axonal-promoting factors were observed in degenerative FJCs surgically obtained from symptomatic subjects. Increased VEGF, (NGF/TrkA), and sensory neuronal distribution were also detected in degenerative FJC tissues from subjects with LBP. qPCR and WB results demonstrated highly upregulated inflammatory cytokines, pain mediators, and cartilage-degrading enzymes in degenerative FJCs. Results from ex vivo co-culture of the DRG and FJC tissue demonstrated that degenerative FJCs increased the expression of inflammatory pain molecules in the sensory neurons. CONCLUSION: Degenerative FJCs possess greatly increased inflammatory and angiogenic features, suggesting that these factors play an important role in the progression of FJD and serve as a link between joint degeneration and neurological stimulation of afferent pain fibers.

Establishment of a rat model of adjuvant-induced osteoarthritis of the lumbar facet joint.

To study the establishment of adjuvant-induced osteoarthritis of the lumbar facet joint in a rat model. Complete Freund's adjuvant (experimental group) and saline (control group) were randomly injected into the right and left side of rat, respectively. The rats were killed, and degeneration of lumbar facet joint was evaluated at macroscopic level and scored based on OARSI scores system. Moreover, Interleukin-1ß and tumor necrosis factor-α levels in the synovium were measured. The macroscopic scores and OARSI scores of experimental group were higher than the control group (P < 0.05). The concentration of tumor necrosis factor-α was significantly increased only on 3- and 7-day post-surgery when compared with controls, and interleukin-1ß was increased on days 3,7 and 14 post-surgery (P < 0.05). The rat model of adjuvant can induce degeneration of the lumbar facet joint. It can be useful for studies on mechanisms and treatment of lumbar facet joint osteoarthritis.

The pathogenesis of psoriatic arthritis and associated nail disease: not autoimmune after all?

PURPOSE OF REVIEW: Both psoriasis and psoriatic arthritis (PsA), and by implication psoriatic nail disease, have been considered as autoimmune disorders. This was based on the assumption that T-cell-directed responses against common skin and synovial antigens led to shared immunopathological mechanisms at these different sites, which was indirectly supported by the human leucocyte antigen-Cw6 disease association. This study draws on recent microanatomical and genetic studies of PsA, psoriasis and psoriatic-associated nail disease to show how the prevailing autoimmunity concepts for psoriatic disease need to be redrawn, especially in the case of joint and nail disease. RECENT FINDINGS: Recent microanatomical studies confirm that normal tendon and ligament insertion points to bone (entheses), the key territory for the inflammatory reaction associated with PsA, being subject to microdamage that strongly points to a role for microtrauma in the joints, which is reminiscent of Koebner responses in the skin. Furthermore, the nail is functionally integrated with entheses associated with the distal phalanx that provides anchorage to the skin and joint. Although type 1 psoriasis is strongly linked to the human leucocyte antigen-Cw6, recent genetic studies have suggested that both joint and nail disease do not share this association. SUMMARY: These microanatomical and genetic insights have important implications for a better understanding of PsA and nail disease and for an improved understanding of the psoriatic disease spectrum.

Correlation of histopathological findings and magnetic resonance imaging in the spine of patients with ankylosing spondylitis.

Ankylosing spondylitis (AS) is a chronic inflammatory disease which affects primarily the sacroiliac joints and the spine. In patients with active disease, magnetic resonance imaging (MRI) of the spine shows areas of bone marrow edema, the histopathological equivalent of which is unknown. In this study we correlate inflammation in the spine of patients with AS as revealed by histological examination with bone marrow edema as detected by MRI. We have compared the histopathological findings of zygapophyseal joints from 8 patients with AS (age: 30 to 64, disease duration 7 to 33 years) undergoing spinal surgery with findings in MRI. For histopathological analysis, we quantified infiltrates of CD3+, CD4+ and CD8+ T cells as well as CD20+ B cells immunohistochemically. Bone marrow edema was evaluated in hematoxylin and eosin stained sections and quantified as the percentage of the bone marrow area involved. All patients with AS showed interstitial mononuclear cell infiltrates and various degrees of bone marrow edema (range from 10% to 60%) in histopathological analysis. However, in only three of eight patients histopathological inflammation and edema in the zygapophyseal joints correlated with bone marrow edema in zygapophyseal joints of the lumbar spine as detected by MRI. Interestingly, two of these patients showed the highest histological score for bone marrow edema (60%). This first study correlating histopathological changes in the spine of patients with AS with findings in MRI scans suggests that a substantial degree of bone marrow inflammation and edema is necessary to be detected by MRI.

Successful short term treatment of severe undifferentiated spondyloarthropathy with the anti-tumor necrosis factor-alpha monoclonal antibody infliximab.

OBJECTIVE: Tumor necrosis factor-alpha (TNF-alpha) has been detected in sacroiliac joints of patients with spondyloarthropathies (SpA). Anti-TNF-a therapy has been efficacious in patients with active ankylosing spondylitis (AS) and psoriatic arthritis. Similar to these SpA subtypes, therapeutic options in undifferentiated SpA (uSpA) are also limited. We tested the efficacy of the monoclonal anti-TNF-alpha antibody infliximab in patients with active and severe uSpA in an open observation trial. METHODS: Six patients with uSpA were treated with 3 infusions of infliximab in a dosage of 3 (n = 3) or 5 mg/kg (n = 3) at Weeks 0, 2, and 6. The total observational period was 12 weeks. The Bath AS Disease Activity Index (BASDAI), the Functional Index (BASFI), pain on a visual analog scale, the Bath AS Metrology Index (BASMI), and quality of life (SF-36) were assessed before, during, and after therapy. RESULTS: Significant improvement at Day 1 after the first infusion lasting until Week 12 was reported by 5/6 patients. Improvement of > or = 50% in all activity, function, pain, and swollen joint scores was observed in the patients taking 5 mg/kg. The 3 mg/kg dose was less effective, resulting in > or = 15% improvement in outcome variables. Peripheral arthritis, enthesitis, and spinal symptoms improved equally. C-reactive protein dropped in 4 patients. Health related quality of life increased. No serious side effects or infections occurred. CONCLUSION: These observations suggest that anti-TNF-alpha therapy has significant short term efficacy in patients with severe uSpA.