Localization of Nerve Growth Factor Expression to Structurally Damaged Cartilaginous Tissues in Human Lumbar Facet Joint Osteoarthritis.

Purpose: Nerve Growth Factor (NGF) is a pivotal mediator of chronic pain and plays a role in bone remodelling. Through its high affinity receptor TrkA, NGF induces substance P (SP) as key downstream mediator of pain and local inflammation. Here we analysed NGF, TrkA and SP tissue distribution in facet joint osteoarthritis (FJOA), a major cause of chronic low back pain. Methods: FJOA specimens (n=19) were harvested from patients undergoing intervertebral fusion surgery. Radiologic grading of FJOA and spinal stenosis, followed by immunohistochemistry for NGF, TrkA and SP on consecutive tissue sections, was performed in ten specimens. Explant cultures (n=9) were used to assess secretion of NGF, IL-6, and SP by FJOA osteochondral tissues under basal and inflammatory conditions. Results: NGF was predominantly expressed in damaged cartilaginous tissues (80%), occasionally in bone marrow (20%), but not in osteochondral vascular channels. NGF area fraction in cartilage was not associated with the extent of proteoglycan loss or radiologic FJOA severity. Consecutive sections showed that NGF and SP expression was localized at structurally damaged cartilage, in absence of TrkA expression. SP and TrkA were expressed in subchondral bone marrow in both presence and absence of NGF. Low level NGF, but not SP secretion, was detected in four out of eighteen FJOA explants under both basal or inflammatory conditions (n=2 each). Conclusion: NGF is associated with SP expression and structural cartilage damage in osteoarthritic facet joints, but not with radiologic disease severity. NGF tissue distribution in FJOA differs from predominant subchondral bone expression reported for knee OA.

Biochemical and biomechanical characterisation of equine cervical facet joint cartilage.

BACKGROUND: The equine cervical facet joint is a site of significant pathology. Located bilaterally on the dorsal spine, these diarthrodial joints work in conjunction with the intervertebral disc to facilitate appropriate spinal motion. Despite the high prevalence of pathology in this joint, the facet joint is understudied and thus lacking in viable treatment options. OBJECTIVE: The goal of this study was to characterise equine facet joint cartilage and provide a comprehensive database describing the morphological, histological, biochemical and biomechanical properties of this tissue. STUDY DESIGN: Descriptive cadaver studies. METHODS: A total of 132 facet joint surfaces were harvested from the cervical spines of six skeletally mature horses (11 surfaces per animal) for compiling biomechanical and biochemical properties of hyaline cartilage of the equine cervical facet joints. Gross morphometric measurements and histological staining were performed on facet joint cartilage. Creep indentation and uniaxial strain-to-failure testing were used to determine the biomechanical compressive and tensile properties. Biochemical assays included quantification of total collagen, sulfated glycosaminoglycan and DNA content. RESULTS: The facet joint surfaces were ovoid in shape with a flat articular surface. Histological analyses highlighted structures akin to articular cartilage of other synovial joints. In general, biomechanical and biochemical properties did not differ significantly between the inferior and superior joint surfaces as well as among spinal levels. Interestingly, compressive and tensile properties of cervical facet articular cartilage were lower than those of articular cartilage from other previously characterised equine joints. Removal of the superficial zone reduced the tissue's tensile strength, suggesting that this zone is important for the tensile integrity of the tissue. MAIN LIMITATIONS: Facet surfaces were sampled at a single, central location and do not capture the potential topographic variation in cartilage properties. CONCLUSIONS: This is the first study to report the properties of equine cervical facet joint cartilage and may serve as the foundation for the development of future tissue-engineered replacements as well as other treatment strategies.

Evaluation of Water Content in Lumbar Intervertebral Discs and Facet Joints Before and After Physiological Loading Using T2 Mapping MRI.

STUDY DESIGN: T2 mapping was used to quantify the water content of lumbar spine intervertebral discs (IVDs) and facet joints before and after physiological loading. OBJECTIVE: The aim of this study was to clarify the interaction between lumbar spine IVD and facet joints as load-bearing structures by measuring the water content of their matrix after physiological loading using T2 mapping magnetic resonance imaging (MRI). SUMMARY OF BACKGROUND DATA: To date, few reports have functionally evaluated lumbar spine IVD and facet joints, and their interaction in vivo. T2 mapping may help detect changes in the water content of IVD and articular cartilage of facet joints before and after physiological loading, thereby enabling the evaluation of changes in interacted water retention between IVD and facet joints. METHODS: Twenty asymptomatic volunteers (10 female and 10 male volunteers; mean age, 19.3 years; age range, 19-20 years) underwent MRI before and after physiological loading such as lumbar flexion, extension, and rotation. Each IVD from L1/2 to L5/S1 was sliced at center of the disc space, and the T2 value was measured at the nucleus pulposus (NP), anterior annulus fibrosus (AF), posterior AF, and bilateral facet joints. RESULTS: In the NP, T2 values significantly decreased after exercise at every lumbar spinal level. In the anterior AF, there were no significant differences in T2 values at any level. In the posterior AF, T2 values significantly increased only at L4/5. In the bilateral facet joints, T2 values significantly decreased after exercise at every level. CONCLUSION: There was a significant decrease in the water content of facet joints and the NP at every lumbar spinal level after dynamic loading by physical lumbar exercise. These changes appear to play an important and interactional role in the maintenance of the interstitial matrix in the IVD NP and cartilage in the facet joint. LEVEL OF EVIDENCE: 3.

Characterization of facet joint cartilage properties in the human and interspecies comparisons.

The facet joint, a synovial joint located on the posterior-lateral spine, is highly susceptible to degenerative changes and plays a significant role in back-related morbidities. Despite its significance, the facet is rarely studied and thus current treatment strategies are lacking. This study aimed to characterize, for the first time, the properties of human, pig, monkey, and rabbit lumbar facet cartilage providing much-needed design criteria for tissue engineering approaches. In this study, where possible, the facet's morphological, histological, mechanical, and biochemical properties were evaluated. Comparisons between the properties of the inferior and superior facet surfaces, as well as among spinal levels were performed within each species. In addition, interspecies comparisons of the properties were determined. The human facet joint was found to be degenerated; 100% of joint surfaces showed signs of pathology and approximately 71% of these were considered to be grade 4. Joint morphology varied among species, demonstrating that despite the mini-pig facet being closest to the human in terms of width and length, it was far more curved than the human or any of the other species. No notable differences were found in the mini-pig, monkey, and rabbit mechanical and biochemical properties, suggesting that these species, despite morphological differences, may serve as suitable animal models for studying structure-function relationships of the human facet joint. The characterization data reported in this study may increase our understanding of this ill-described joint as well as provide the foundation for the development of new treatments such as tissue engineering. STATEMENT OF SIGNIFICANCE: This work provides the first comprehensive description of the properties of lumbar facet joint cartilage. Importantly, this work establishes that histological, biochemical, and mechanical properties are comparable between bipedal and quadrupedal animals, helping to guide future selection of appropriate animal models. This work also suggests that the human facet joint is highly susceptible to pathology. The mechanical properties of facet cartilage, found to be inferior to those of other synovial joints, provide a greater understanding of the joint's structure-function relationships as well as the potential etiology of facet joint pathology. Lastly, this work will serve as the foundation for the development of much-needed facet joint treatments, especially those based on tissue engineering approaches.

Stretch-induced network reconfiguration of collagen fibres in the human facet capsular ligament.

Biomaterials can display complex spatial patterns of cellular responses to external forces. Revealing and predicting the role of these patterns in material failure require an understanding of the statistical dependencies between spatially distributed changes in a cell's local biomechanical environment, including altered collagen fibre kinematics in the extracellular matrix. Here, we develop and apply a novel extension of network science methods to investigate how excessive tensile stretch of the human cervical facet capsular ligament (FCL), a common source of chronic neck pain, affects the local reorganization of collagen fibres. We define collagen alignment networks based on similarity in fibre alignment angles measured by quantitative polarized light imaging. We quantify the reorganization of these networks following macroscopic loading by describing the dynamic reconfiguration of network communities, regions of the material that display similar fibre alignment angles. Alterations in community structure occur smoothly over time, indicating coordinated adaptation of fibres to loading. Moreover, flexibility, a measure of network reconfiguration, tracks the loss of FCL's mechanical integrity at the onset of anomalous realignment (AR) and regions of AR display altered community structure. These findings use novel network-based techniques to explain abnormal collagen fibre reorganization, a dynamic and coordinated multivariate process underlying tissue failure.

Is There any Correlation Between Pathological Profile of Facet Joints and Clinical Feature in Patients With Thoracolumbar Kyphosis Secondary to Ankylosing Spondylitis?: An Immunohistochemical Investigation.

STUDY DESIGN: An immunohistochemical analysis. OBJECTIVE: The aim of this study was to systematically and extensively evaluate the immunopathology of the facet joints in patients with thoracolumbar kyphosis secondary to ankylosing spondylitis (AS). SUMMARY OF BACKGROUND DATA: The facet joints may be predominantly involved in the process of spinal inflammation in AS. Thus, a detailed investigation of the immunopathology at sites of facet joints is of crucial importance in understanding the pathogenesis of AS. METHODS: The facet joints were obtained from 30 AS patients and 23 age- and gender-matched controls (patients with fresh thoracolumbar fracture). The facet joints were assessed immunohistochemically by analyzing the number of infiltrating T cells (CD3, CD4, CD8), B cells (CD20), microvessel density (CD34), osteoblasts (CD56), bone marrow macrophages (CD68), and osteoclasts (CD68) per high-power field (hpf). According to the presence or absence of persistent inflammation, AS patients were divided into 2 groups: A (patients with persistent inflammation) and B (patients without persistent inflammation). Lumbar spinal mobility was assessed using the modified Schober index (MSI). RESULTS: Two or more CD3+ T cell aggregates were found in the facet joints from 18 of 30 AS patients, whereas 1 CD3+ T cell aggregate was noted in 5 of 23 patients with thoracolumbar fracture. The levels of T cells (CD4+ and CD8+), CD20+B cells, CD56+ osteoblasts, and CD34+ microvessel density were significantly higher in AS patients than in the controls (all P < 0.01). Notably, the MSI score in group A was significantly higher than that in group B (P < 0.01). CONCLUSION: Active spinal inflammation is frequently observed in AS patients with thoracolumbar kyphosis. In addition, persistent inflammation in facet joints may further contribute to the loss of spinal mobility in the later stages of AS. These findings indicate that careful monitoring of disease activity is mandatory for AS patients in its advanced stage. LEVEL OF EVIDENCE: 4.

[An imaging study on location of the anterior border of facets and the posterior border of vertebral bodies in lower cervical spine].

OBJECTIVE: To explore the location of the anterior border of facets and the posterior border of vertebral bodies in lower cervical spine,and to provide a quantitative data to evaluate the correct length of transarticual screws in lower cervical spine during procedure. METHODS: One hundred standard lateral X-ray films and fifty CT films on cervical spine were used to measure the distance of the anterior border of facets and the posterior border of vertebral bodies in lower cervical spine. HS, HM and HI were defined as parameters, which means the distance between the anterior border of the superior (HS), median (HM) and inferior (HI) part of facets and the posterior border of corresponding vertebral bodies. The value will be negative if the anterior border of the facet located before the vertebral body. RESULTS: 'HS > HM > HI' was found in all facets in lower cervical spine. The anterior border of the facet in C(3,4) located before the posterior border of the vertebral body of C3. The anterior border of C(4,5) and C(5,6) was inclined to posterior. The anterior border of C(6,7) located after the posterior border of the vertebral body of C6. The pattern of HS increased from C(3,4) to C(6,7), the minimal (0 +/- 0.25) mm and the maximal (2.91 +/- 1.05) mm. The tendency of HM raised from C(3,4) to C(6,7), the minimal (-1.57 +/- 0.53) mm and the maximal (1.54 +/- 0.39) mm. The pattern HI added from C(3,4) to C(6,7), the minimal (-2.03 +/- 0.40) mm and the maximal (1.08 +/- 0.70) mm. CONCLUSION: During the implantation of the transarticular screws, the tip of the screws should be 0-2 mm before the posterior border of the vertebral body of C3 at C(3,4), 0-2 mm after that of C4 at C(4,5), 0.5-2.5 mm at C(5,6) and 1-3 mm at C(6,7). The quantitative location between the anterior border of facets and the posterior border of the corresponding vertebral bodies can offer an indirect method to evaluate the correct length of transarticual screws in lower cervical spine during procedure.

Inflammatory cytokines released from the facet joint tissue in degenerative lumbar spinal disorders.

STUDY DESIGN: A prospective study of surgical cases of degenerative lumbar spinal disorders demonstrated inflammatory cytokines in the facet joint tissue. OBJECTIVE: To quantify various inflammatory cytokines released from the facet joint tissue in surgical cases of degenerative lumbar spinal disorders. SUMMARY OF BACKGROUND DATA: In degenerative lumbar spinal disorders, pain is often caused by osteoarthritis of a facet joint. There are inflammatory mediators such as prostaglandins and leukotrienes in facet joint tissue in lumbar spinal degeneration. However, no reports have studied if there are also inflammatory cytokines in the facet joint, which generated arthropathic changes in degenerative lumbar spinal disorder and if pain is caused by chemical factors associated with inflammation such as inflammatory cytokines. METHODS: Forty patients with degenerative lumbar disorders who had undergone operative treatment were included in this study. Fifty-five joint cartilages and 67 synovia were harvested from the lumbar facet joints in responsible intervertebral levels of patients. There were 24 male and 16 female subjects with average ages of 50 and 67 years, respectively, in 11 cases of lumbar disc herniation and 29 cases of lumbar spinal canal stenosis. Using ELISA and CLEIA methods, joint cartilage and synovial tissues were harvested during surgery from the facet joint at the responsible upper levels to measure IL-1beta, TNF-alpha, and IL-6 in individual tissues. RESULTS: IL-1beta was detected in joint cartilage and synovium in both groups and its positive reaction rate was higher in LSCS than in LDH. There was no difference in IL-1beta concentration in cartilage tissue between the two groups. There was TNF-alpha in the synovium of LSCS. IL-6 was high in joint cartilage and synovium in both groups. The concentration was significantly higher in LSCS than in LDH. CONCLUSIONS: There are inflammatory cytokines in facet joint tissue at high levels in degenerative lumbar spinal disorders. Inflammatory cytokines have a higher concentration rate in lumbar spinal canal stenosis than in lumbar disc herniation. This finding suggests that inflammatory cytokines in degenerated facet joints may have some relation to the cause of pain in degenerative lumbar disorders.