Relationship between cartilage glycosaminoglycan content (assessed with dGEMRIC) and OA risk factors in meniscectomized patients

SummaryObjectiveTo study the relationship between cartilage integrity, assessed with [delayed Gadolinium-Enhanced Magnetic Resonance Imaging of Cartilage (dGEMRIC)] and epidemiologic risk factors for knee osteoarthritis (OA) in meniscectomized patients.MethodsBody mass index (BMI) was calculated in 45 patients (16 women), mean age 46, who underwent an arthroscopic medial meniscectomy 1–6 years earlier. The cartilage glycosaminoglycan (GAG) content was estimated by dGEMRIC Index and tests of isokinetic muscle strength and functional performance (one-leg hop test) were conducted.ResultsBMI ranged from 20.0 to 34.3 (mean: 26.5). The dGEMRIC Index was 14.4% lower in the medial index compartment (374±61ms, mean±SD) than in the lateral reference compartment (437±59ms, mean±SD) (P<0.001).The dGEMRIC Index of the medial diseased compartment correlated positively with both knee flexor (r=0.50, P=0.001) and knee extensor strength (r=0.47, P=0.001) relative to body weight and with the one-leg hop test (r=0.42, P=0.004). Furthermore, a negative correlation was found between the dGEMRIC Index of the medial compartment and BMI (r=−0.35, P=0.019).No significant correlations were found in the lateral reference compartment.ConclusionThe lower dGEMRIC Index of the medial compartment suggests decreased cartilage GAG content after medial meniscectomy, indicating an early stage OA. Furthermore, results suggest that overweight is a factor that deteriorates cartilage, whereas strong and co-ordinated thigh muscles may have a protective effect on the cartilage integrity

Intra-Articular Fms-Like Tyrosine Kinase 3 Ligand Expression Is a Driving Force in Induction and Progression of Arthritis

Background: One of the hallmarks of rheumatoid arthritis (RA) is hyperplasia and inflammation of the synovial tissue being characterized by in situ occurrence of highly differentiated leukocytes. Fms-like tyrosine kinase 3 (Flt3) has a crucial role in hematopoiesis, regulation of cell proliferation, differentiation and apoptosis. Typically, Flt3 is expressed on early myeloid and lymphoid progenitors and is activated by its soluble ligand (Flt3-L). The highly differentiated cellular pattern in the synovium of the RA patients made us hypothesize that Flt3-L, with its ability to induce proliferation and differentiation, could be of importance in induction and/or progression of arthritis. Methodology/Principal Findings: To investigate occurrence of Flt3-L in RA we have measured its levels in matched serum and synovial fluid samples from 130 patients and 107 controls. To analyse the pro-inflammatory role of Flt3-L, we continuously overexpressed this protein locally in healthy mouse joints using homologous B-cell line transfected with Flt3-L gene. Additionally, recombinant Flt3-L was instillated intra-articularly in combination with peptidoglycans, a Toll Like Receptor 2-ligand with stong arthritogenic properties. Our results show significantly higher levels of Flt3-L in the synovial fluid as compared to serum levels in RA subjects (p = 0.0001). In addition, RA synovial fluid levels of Flt-3-L were significantly higher than these obtained from synovial fluids originating from non-inflammatory joint diseases (p = 0.022). Intra-articular administration of B-cell line transfected with Flt3-L gene resulted in highly erosive arthritis while inoculation of the same B-cell line without hyperexpression of Flt3-L did not induce erosivity and only in a minority of cases caused synovial proliferation! Flt3-ligand potentiated peptidoglycan induced arthritis as compared to mice injected with peptidoglycan alone (p<0.05). Conclusions/Significance: Our findings indicate that Flt3-L is strongly expressed at the site of inflammation in human RA. It exerts both pro-inflammatory and tissue destructive properties once in the joint cavity. Owing to these properties, treatment attempts to neutralize this molecule should be considered in RA

Long-term effect of removal of knee joint loading on cartilage quality evaluated by delayed gadolinium-enhanced magnetic resonance imaging of cartilage

SummaryObjectiveAnkle fracture patients were used as a model to study the long-term effect of the removal of joint loading on knee cartilage quality in human subjects.DesignThe knees of 10 patients with ipsilateral ankle fractures were investigated using delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC) at the time of ankle injury. After 6 weeks' prescribed unloading of the affected leg, but no restrictions regarding knee movement, the cast was removed from the ankle and the patient underwent a second dGEMRIC examination. Physiotherapy was then initiated. A third dGEMRIC examination was performed 4 months after remobilization, and a final examination 1 year after the injury.ResultsBaseline T1Gd values for the 10 patients were within a narrow range. No significant change in mean T1Gd was observed after 6 weeks' prescribed unloading, but the T1Gd range had increased significantly. Four months after remobilization, the mean T1Gd was significantly lower than in the previous examinations, and the range remained significantly broader than at baseline. At the 1-year follow-up, the mean T1Gd was almost identical to the value after remobilization, and the T1Gd range still showed a significant increase compared to the baseline investigation.ConclusionsRemoval of knee cartilage loading for 6 weeks resulted in a measurable effect on the cartilage matrix, as evidenced by a broader T1Gd range. A decrease in mean T1Gd was observed 4 months after remobilization. These differences persisted a year after injury compared to baseline