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Osteoarthritis is a type of joint disease that may lead to other joint diseases. Previous research has demonstrated that tumor necrosis factor (TNF)‑α is associated with osteoarthritis activity and pathology. The possible mechanisms of the TNF‑α‑mediated signaling pathway have not been clearly elaborated in synovial fibroblasts. The present study aimed to investigate the potential mechanisms of TNF‑α in a mouse model of iodoacetate‑induced osteoarthritis. Reverse transcription‑quantitative polymerase chain reaction, ELISA, western blotting and immunohistochemistry were performed to evaluate the role of TNF‑α in the progression of osteoarthritis. The results revealed that the serum levels of TNF‑α, interleukin (IL)‑1β, IL‑4 and IL‑6 were significantly upregulated in a mouse model of iodoacetate‑induced osteoarthritis compared with healthy mice (P<0.01). TNF‑α, IL‑1β, IL‑4 and IL‑6 mRNA and protein levels were also significantly upregulated in synovial fibroblasts in the experimental mice (P<0.01). It was demonstrated that TNF‑α increased pro‑inflammation factors matrix metalloproteinase (MMP)‑3, MMP‑9, nuclear factor (NF)‑κB and receptor activator of NF‑κB ligand (RANKL) in synovial fibroblasts. It was also observed that the toll‑like receptor (TLR)‑3 was significantly upregulated and extracellular signal‑regulated kinase (ERK) and protein kinase B (AKT) were significantly downregulated in synovial fibroblasts in osteoarthritis mice (P<0.01). An in vitro assay demonstrated that TNF‑α inhibitor decreased mRNA and protein levels of IL‑1β, IL‑4 and IL‑6 in synovial fibroblasts. The knockdown of TLR‑3 abolished the TNF‑α upregulated mRNA and protein levels of IL‑1β, IL‑4 and IL‑6 in synovial fibroblasts. In addition, the knockdown of TLR‑3 also reversed TNF‑α‑upregulated ERK and AKT expression in synovial fibroblasts. In vivo assays demonstrated that TNF‑α inhibitor significantly decreased the deposition of IL‑1β, IL‑4 and IL‑6 as well as bone destruction and significantly increased the body weight and osteoarthritis score for osteoarthritic mice (P<0.01). TNF‑α inhibitor decreased TLR‑3 and significantly increased the expression and phosphorylation of ERK and AKT in articular cartilage (P<0.01). In conclusion the results of the present study indicate that TNF‑α serves an essential role in synovial fibroblasts in osteoarthritis, suggesting that inhibition of TNF‑α may decrease inflammation via the TLR‑3‑mediated ERK/AKT signaling pathway in a mouse model of monosodium iodoacetate‑induced osteoarthritis.

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AimThis study aims to quantitatively analyze the changes in local microcirculation in early osteonecrosis of the femoral head (ONFH) by dynamic contrast-enhanced (DCE) MRI and to explore the pathophysiological mechanisms of early ONFH.Patients and MethodsWe selected 49 patients (98 hips) aged 21–59 years who were clinically diagnosed with early ONFH. A total of 77 femoral heads were diagnosed with different degrees of necrosis according to the Association Research Circulation Osseous (ARCO) staging system, and 21 femoral heads were judged to be completely healthy. All patients underwent DCE-MRI scanning. Pseudocolor images and time-signal intensity curves were generated by Tissue 4D processing software. The volume transfer constant (Ktrans), extracellular extravascular space, also known as vascular leakage (Ve), and transfer rate constant (Kep) of healthy and different areas of necrotic femoral heads were measured on perfusion parameter maps. The differences and characteristics of these parameters in healthy and different areas of necrotic femoral heads were analyzed.ResultsThe signal accumulation in healthy femoral heads is lower than that of necrotic femoral heads in pseudocolor images. The time-signal intensity curve of healthy femoral heads is along the horizontal direction, while they all have upward trends for different areas of necrotic femoral heads. The mean value of Ktrans of healthy femoral heads was lower than the integration of necrotic, boundary, and other areas (F = 3.133, P = .036). The Kep value of healthy femoral heads was higher than the integration of lesion areas (F = 6.273, P = .001). The mean Ve value of healthy femoral heads was smaller than that of the lesion areas (F = 3.872, P = .016). The comparisons of parameters between different areas and comparisons among healthy areas and lesion areas showed different results.ConclusionONFH is a complex ischemic lesion caused by changes in local microcirculation. It mainly manifests as increased permeability of the vascular wall, blood stasis in the posterior circulation, high intraosseous pressure in the femoral head, and decreased arterial blood flow. The application of DCE-MRI scanning to quantitatively analyze the visual manifestations of microcirculation after early ONFH is an ideal method to study the microcirculation changes of necrotic femoral heads.