Dickkopf-1 (Dkk-1) in plasma and synovial fluid is inversely correlated with radiographic severity of knee osteoarthritis patients

<p>Abstract</p> <p>Background</p> <p>Osteoarthritis (OA) is a common degenerative joint disease causing pain, stiffness, reduced motion, swelling, crepitus, and disability. Dickkopf-1 (Dkk-1) is a critical mediator of osteoblastogenesis and regulates the joint remodeling. The aim of this study was to examine plasma and synovial fluid Dkk-1 levels of patients with primary knee OA and to investigate their relationship with disease severity.</p> <p>Methods</p> <p>Thirty-five patients aged 55-83 years with knee OA and 15 healthy individuals were recruited into this study. Disease severity was determined using weight-bearing anteroposterior radiographs of the affected knee. The radiological grading of OA in the knee was performed according to the Kellgren-Lawrence grading system. Dkk-1 levels in both plasma and synovial fluid were evaluated using enzyme-linked immunosorbent assay.</p> <p>Results</p> <p>The average concentration of circulating Dkk-1 in the knee OA patients was remarkably lower than that of healthy controls (396.0 ± 258.8, 95%CI 307.1-484.9 vs 2348.8 ± 2051.5, 95%CI 1164.3-3533.3 pg/ml, p < 0.0001). Dkk-1 levels in synovial fluid were significantly lower than in paired plasma samples (58.6 ± 31.8, 95%CI 47.7-69.6 vs 396.0 ± 258.8, 95%CI 307.1-484.9 pg/ml, p < 0.001). Furthermore, both plasma and synovial fluid Dkk-1 levels were inversely correlated with radiographic severity (r = -0.78, p < 0.001 and r = -0.42, p = 0.01, respectively). Plasma Dkk-1 levels were also significantly correlated with synovial fluid Dkk-1 levels (r = 0.72, p < 0.001).</p> <p>Conclusions</p> <p>Dkk-1 levels in plasma and synovial fluid are inversely related to the severity of joint damage in knee OA. Dkk-1 could serve as a biochemical marker for determining disease severity and might play a potential role in the pathogenesis of the degenerative process of OA.</p

Immune Mediators in Osteoarthritis: Infrapatellar Fat Pad-Infiltrating CD8+ T Cells Are Increased in Osteoarthritic Patients with Higher Clinical Radiographic Grading

Osteoarthritis is a condition of joint failure characterized by many pathologic changes of joint-surrounding tissues. Many evidences suggest the role of both innate and adaptive immunity that interplay, resulting either in initiation or in progression of osteoarthritis. Adaptive immune cells, in particular T cells, have been demonstrated to play a role in the development of OA in animal models. However, the underlying mechanism is yet unclear. Our aim was to correlate the frequency and phenotype of tissue-infiltrating T cells in the synovial tissue and infrapatellar fat pad with radiographic grading. Our results show that CD8+ T cells are increased in osteoarthritic patients with higher radiographic grading. When peripheral blood CD8+ T cells were examined, we show that CD8+ T cells possess a significantly higher level of activation than its CD4+ T cell counterpart (P<0.0001). Our results suggest a role for CD8+ T cells and recruitment of these activated circulating peripheral blood CD8+ T cells to the knee triggering local inflammation within the knee joint

Relationships between blood leukocyte mitochondrial DNA copy number and inflammatory cytokines in knee osteoarthritis.

Osteoarthritis (OA) is a degenerative articular disorder manifested by cartilage destruction, subchondral sclerosis, osteophytes, and synovitis, resulting in chronic joint pain and physical disability in the elderly. The purpose of this study was to investigate mitochondrial DNA copy number (mtDNACN) and inflammatory cytokines in primary knee OA patients and healthy volunteers. A total of 204 knee OA patients and 169 age-matched healthy volunteers were recruited. Their relative blood leukocyte mtDNACN was assessed by quantitative real-time polymerase chain reaction (qRT-PCR), and ten inflammatory cytokines in their plasma were detected by multiplex immunoassay. Blood leukocyte mtDNACN in the OA group was significantly lower than that in the control group. Leukocyte mtDNACN in the control group was negatively correlated with their age (r=-0.380, P<0.0001), whereas mtDNACN in the OA group was positively correlated with their age (r=0.198, P<0.001). Plasma interleukin-4 (IL-4) and IL-6 were significantly higher in the knee OA group than in the control group. The plasma IL-6 level was positively correlated with blood leukocyte mtDNACN in the OA group (r=0.547, P=0.0014). IL-5 showed as a major factor (coefficient 0.69) in the second dimension of principle components analysis (PCA)-transformed data and was significantly higher in the OA group (P<0.001) as well as negatively correlated with mtDNACN (r=-0.577, P<0.001). These findings suggest that elevation of plasma IL-4 and IL-6 and a relative reduction in mtDNACN might be effective biomarkers for knee OA. IL-5 is a plausible factor responsible for decreasing blood leukocyte mtDNACN in knee OA patients

Vitamin D Supplementation Improves Quality of Life and Physical Performance in Osteoarthritis Patients

(1) Background: Lower levels of serum 25-hydroxyvitamin D (25(OH)D) are common in osteoarthritis (OA) patients. However, the effect of vitamin D supplementation on muscle strength and physical performance remains unclear. This study will investigate the effects of vitamin D2 supplementation on muscle strength and physical performance in knee OA patients; (2) Methods: One hundred and seventy-five primary knee OA patients with low levels of serum 25(OH)D (&lt;30 ng/mL) received 40,000 IU vitamin D2 (ergocalciferol) per week for six months. Body composition, muscle strength, physical performance, serum 25(OH)D level, leptin, interlukin-6 (IL-6), parathyroid hormone (PTH), protein carbonyl, and metabolic profile were analyzed; (3) Results: Baseline mean serum 25(OH)D levels in knee OA patients was 20.73 ng/mL. Regarding baseline vitamin D status, 58.90% of patients had vitamin D insufficiency, and 41.10% had vitamin D deficiency. After vitamin D2 supplementation for six months, mean serum 25(OH)D level was 32.14 ng/mL. For post-supplementation vitamin D status, 57.10% of patients had vitamin D sufficiency and 42.90% had vitamin D insufficiency. From baseline to six months, there was a significant increase in mean serum 25(OH)D level (p &lt; 0.001), while mean LDL cholesterol (p = 0.001), protein carbonyl (p = 0.04), and PTH (p = 0.005) all significantly decreased. Patient quality of life (SF-12) and pain (visual analog scale, VAS) both improved significantly from baseline to the six-month time point (p = 0.005 and p = 0.002, respectively). Knee OA patients demonstrated significant improvement grip strength and physical performance measurements after vitamin D2 supplementation (p &lt; 0.05); (4) Conclusions: Vitamin D2 supplementation for six months reduced oxidative protein damage, decreased pain (VAS), improved quality of life, and improved grip strength and physical performance in osteoarthritis patients

Effect of vitamin E on oxidative stress level in blood, synovial fluid, and synovial tissue in severe knee osteoarthritis: a randomized controlled study

Abstract Background This study was performed to evaluate the antioxidative and anti-inflammatory effects of vitamin E on oxidative stress in the plasma, synovial fluid, and synovial tissue of patients with knee osteoarthritis. Methods Seventy-two patients with late-stage knee osteoarthritis scheduled for total knee arthroplasty were randomized to take oral placebo (Group A) or 400 IU of vitamin E (Group B) once a day for 2 months before undergoing surgery. The blood levels of endpoints indicating oxidative stress or antioxidant capacity, Knee Society Score (KSS), Western Ontario and McMaster Universities Osteoarthritis Index score (WOMAC), and adverse effects were compared before and after the intervention between the two groups. At surgery, these redox endpoints and histological findings were compared between the synovial fluid and synovial tissue. Results In blood samples, the pre-intervention of oxidative stress and antioxidative capacity were not different between Group A and Group B. In post-intervention blood samples, the Malondialdehyde (Group A 1.34 ± 0.10, Group B 1.00 ± 0.09, p < 0.02), Alpha tocopherol (Group A 15.92 ± 1.08, Group B 24.65 ± 1.47, p < 0.01) and Trolox equivalent antioxidant capacity (Group A 4.22 ± 0.10, Group B 5.04 ± 0.10, 0 < 0.01) were significantly different between Group A and Group B. In synovial fluid samples, the Malondialdehyde (Group A 1.42 ± 0.12, Group B 1.06 ± 1.08, p 0.01), Alphatocopherol (Group A 4.51, Group B 7.03, p < 0.01), Trolox equivalent antioxidant capacity (Group A, 1.89 ± 0.06, Group B 2.19 ± 0.10) were significantly different between Group A and Group B. The pre-intervention WOMAC score and KSS score were not different between Group A and Group B. The post-intervention WOMAC score was significantly improved in all categories in Group B (Pain: Group A 27.26 ± 0.89, Group B 19.19 ± 1.43, p < 0.01; Stiffness: Group A 8.23 ± 0.79, Group B 5.45 ± 0.73, p 0.01; Function: Group A 94.77 ± 4.22, Group B 72.74 ± 6.55, p < 0.01). The post-intervention KSS score was significantly improved in all categories in Group B (Clinical: Group A 25.31 ± 14.33, Group B 33.52 ± 16.96, p < 0.01; Functional: Group A 41.43 ± 16.11, Group B 51.61 ± 19.60, p 0.02). Significantly fewer synovial tissue cells were stained with nitrotyrosine and hematoxylin–eosin in Group B than in Group A. There were no differences in adverse effects or surgical complications between the groups. Conclusion Vitamin E is an effective antioxidant that can improve clinical symptoms and reduce oxidative stress conditions in patients with late-stage knee osteoarthritis. Trial registration This research project had been approved for registration at Thai Clinical Trials Registry (TCTR) since 2016–08-28 11:26:32 (Retrospective registered). The TCTR identification number is TCTR20160828001

Cytokine Profiling and Intra-Articular Injection of Autologous Platelet-Rich Plasma in Knee Osteoarthritis

Osteoarthritis (OA) is a degenerative joint disease leading to joint pain and stiffness. Due to lack of effective treatments, physical and psychological disabilities caused by OA have a detrimental impact on the patient&rsquo;s quality of life. Emerging evidence suggests that intra-articular injection of platelet-rich plasma (PRP) may provide favorable results since PRP comprises not only a high level of platelets but also a huge amount of cytokines, chemokines, and growth factors. However, the precise mechanism and standardization method remain uncertain. This study aimed to examine cytokine profiling in both PRP and platelet-poor plasma (PPP) of knee OA patients and to determine the effects of PRP on OA chondrocytes and knee OA patients. PRP contained a wide variety of cytokines, chemokines, growth factors, and autologous intra-articular PRP injection resulted in favorable outcomes in knee OA patients. Significant increases in levels of IL-1, IL-2, IL-7, IL-8, IL-9, IL-12, TNF-&alpha;, IL-17, PDGF-BB, bFGF, and MIP-1&beta; were detected in PRP compared to PPP (p &lt; 0.001). An in vitro study showed a marked increase in proliferation in OA chondrocytes cultured with PRP, compared to PPP and fetal bovine serum (p &lt; 0.001). In a clinical study, knee OA patients treated with PRP showed improvement of physical function and pain, assessed by physical performance, Western Ontario and McMaster Universities Arthritis Index and visual analog scale. Our findings from both in vitro and clinical studies suggest that intra-articular PRP injection in knee OA patients may be a potential therapeutic strategy for alleviating knee pain and delaying the need for surgery