Summary Objectives To investigate the association of ultrasound (US) features with pain and the functional scores in patients with equal radiographic grades of osteoarthritis (OA) in both knees. ...Methods Fifty-six consecutive patients with knee OA: 85 symptomatic knees (81 knees with medial pain) and 27 asymptomatic knees, and 10 healthy patients without knee OA as a control were enrolled. US was done by two ultrasonographers blinded to patient diagnoses. US features were semiquantitatively scored (0–3) when appropriate. Results In the OA group, common US findings were marginal osteophyte, suprapatellar synovitis, suprapatellar effusion (SPE), medial meniscus protrusion, medial compartment synovitis (MCS), lateral compartment synovitis, and Baker's cyst. Only SPE and MCS were significantly associated with knee pain. Visual analog pain scale (VAS) scores on motion were positively linearly associated with SPE and MCS ( P < 0.01). Only MCS was degree-dependently associated with VAS scores at rest, the Western Ontario and McMaster Universities pain subscale, and the presence of medial knee pain ( P < 0.01) after adjustments for age, gender, body mass index (BMI), radiographic grade, and other US features. In the control group, no US features were associated with knee pain. Conclusions US inflammation features, including SPE and MCS, were positively linearly associated with knee pain in motion. MCS was also degree-dependently associated with pain at rest and the presence of medial knee pain. These findings show that synovitis was one important predictive factor of pain. Further studies to confirm the association of US features and pain are warranted.
Summary Objective Immune cells are involved in the pathogenesis of osteoarthritis (OA). We examined the effects of T helper (Th) cells, which induce the expression of macrophage inflammatory protein ...(MIP-1γ), on the progression of OA. Design Using anterior cruciate ligament-transection (ACLT), we induced OA in one hind-leg knee joint of B6 mice. The CD4+ T cells from splenocytes and synovium were flow-cytometrically and immunochemically evaluated, respectively. The knee joints were histologically assessed for manifestations of OA. MIP-1γ levels and nuclear factor-κB (NF-κB) in the knee joints were measured using enzyme-linked immunosorbent and immunoblotting assays, respectively; osteoclastogenesis was detected by tartrate-resistant acid phosphatase (TRAP) staining. The inflammatory responses and MIP-1γ expression were examined using immunohistochemistry. Results The number of CD4+ T cells and the expression of interferon-γ (IFN-γ) increased during OA onset (30 days after ACLT) and then decreased at a later stage of OA (90 days after ACLT). Tissue damage induced by CD4+ T cells was evident at the later stage. The activation of CD4+ T cells induced the expression of MIP-1γ and NF-κB. The expression of MIP-1γ can be detected in synovium which CD4+ T cells were infiltrated. The increased MIP-1γ expression caused an increase in the number of osteoclasts in joints. The regulation of CD4+ T cells was accompanied by increased macrophage infiltration and matrix metalloproteinase (MMP)-9 expression. Histopathological examinations revealed that CD4+ T cell knockout (CD4−/− ) mice had less expression of MIP-1γ and slower cartilage degeneration than control mice had. Conclusions CD4+ T cells were activated during the onset of OA, but cartilage damage was more prominent at a later stage. CD4+ T cells were involved in the pathogenesis of OA: they induced MIP-1γ expression and subsequent osteoclast formation.
Cigarette smoking has a negative impact on the skeletal system, causes a decrease in bone mass in both young and old patients, and is considered a risk factor for the development of osteoporosis. In ...addition, it disturbs the bone healing process and prolongs the healing time after fractures. The mechanisms by which cigarette smoking impairs fracture healing are not fully understood. There are few studies reporting the effects of cigarette smoking on new blood vessel formation during the early stage of fracture healing. We tested the hypothesis that cigarette smoke inhalation may suppress angiogenesis and delay fracture healing.
We established a custom-made chamber with airflow for rats to inhale cigarette smoke continuously, and tested our hypothesis using a femoral osteotomy model, radiograph and microCT imaging, and various biomechanical and biological tests.
In the smoking group, Western blot analysis and immunohistochemical staining revealed less expression of vascular endothelial growth factor (VEGF) and von Willebrand factor (vWF). The smoking group also had a lower microvessel density than the control group. Image and biochemical analysis also demonstrated delayed bone healing.
Cigarette smoke inhalation was associated with decreased expression of angiogenic markers in the early bone healing phase and with impaired bone healing.
2020;9(3):99-107.
Emerging evidence has indicated that the perturbed expression of homocysteine (Hcy) may induce mitochondrial dysfunction and disturb bone metabolism. Sirtuin 1 (SIRT1) and AMP-activated protein ...kinase (AMPK) are two critical sensors that regulate mitochondrial biogenesis and have been recognized as therapeutic targets in osteoarthritis (OA). This study was designed to test whether Hcy caused pro-osteoarthritic changes through modulation of SIRT1 and AMPK. Our results showed that administration of Hcy reduced the SIRT1/AMPK/PGC-1α signaling in chondrocytes, leading to mitochondrial dysfunction as a result of increased oxidative stress and apoptosis. Moreover, we demonstrated that the expression of NF-κB, COX-2, IL-8, and MMP-13 were elevated subsequent to inhibition of SIRT1/AMPK/PGC-1α/PPAR-γ pathway by homocysteine, thereby causing detrimental effects on chondrocytes. In the animal model of diet-induced hyperhomocysteinemia (HHcy), we observed the similar findings that SIRT1/PGC-1α/PPAR-γ cascades were downregulated with elevated MMP-13 and COX-2. Taken together, data from the current study revealed that the reduced SIRT1 by Hcy may contribute to degradative cartilage process, which provided insight into the etiology of OA.
•Homocysteine-reduced SIRT1 leads to downregulation of phosphorylated AMPK and PGC-1α.•Homocysteine-inhibited SIRT1 results in mitochondrial dysfunction.•Homocysteine-induced oxidative stress is reversed by activation of SIRT1/AMPK/PGC-1α signaling.•Homocysteine-induced pro-apoptosis effect is rescued by overexpression of SIRT1/AMPK/PGC-1α cascades.•Expression levels of pro-inflammatory mediators and MMP13 are elevated subsequent to suppression of PPAR-γ by homocysteine.
Despite known detrimental effects on the blood flow and histology of nerves after intraneural corticosteroid injection, the neurotoxic effect of corticosteroids remains unclear. We investigated the ...effect of topical dexamethasone on nerve function. Two sponge strips soaked with dexamethasone at doses of 0.8, 1.6, and 3.2 mg were placed under and over the left sciatic nerve of adult Wistar rats for 30 minutes. Mixed-nerve-elicited somatosensory evoked potentials and dermatomal somatosensory evoked potentials were evaluated immediately and repeated together with functional tests and histology 2 weeks later. Evoked potential amplitude was dose-dependently lower and latency was prolonged in dexamethasone-treated sciatic nerves compared to controls. The suppression persisted with incomplete recovery for at least 4 hours, but differences between treated and control nerves were not significant after 2 weeks. Topical dexamethasone adversely affected neural conduction in a dose-dependent manner. Our results suggest that caution is required when using large doses of corticosteroid for injection of the carpal tunnel.
We sought to determine the possible neural conduction blockade of tramadol and whether there is evidence of localized neural toxicity with spinal somatosensory evoked potential (SSEP) measurements. ...Male Wistar rats were used. SSEP, elicited by supramaximally stimulating the hind paw and recorded from the thoracolumbar and the first and second lumbar interspinous ligaments, was monitored. SSEPs were obtained before drug application as the pretreatment baseline and measured every 15 min after treatment for 2 h and at 60-min intervals thereafter until SSEP returned to baseline or for another 4 h. Two small strips of Gelfoam (0.6 × 1.0 cm) soaked with the drug were placed under and over the left sciatic nerve for a 30-min period. Gelfoam was prepared with tramadol hydrochloride (Tramal; the US trade name is Ultram) 5, 2.5, and 1.25 mg, diluted if needed with saline to a total volume of 100 μL (5%, 2.5%, and 1.25%, respectively). The control data were obtained from the right side limb with normal saline by following the same method. Spinal SSEPs were measured after 48 h to detect the late neural damage. The results showed that direct tramadol application on sciatic nerves dose-dependently reduced both the amplitude and conduction velocity of SSEPs when compared with the pretreatment baseline. All SSEPs returned to pretreatment baseline, and no significant changes of SSEP between bilateral limbs were noted at the 48-h measurements. No evidence of irreversible conduction blockade indicative of local neural toxicity was seen. Pretreatment with naloxone 1 mg/kg failed to block the changes of SSEP produced by 2.5% tramadol 100 μL. We conclude that tramadol exerts a local anesthetic–type effect on peripheral nerves.
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