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The aim of the present study was to investigate the effects of phosphorylated osteopontin (p-OPN) on apoptosis and pro-inflammatory cytokine expression in human knee osteoarthritis (OA) chondrocytes. Human knee OA chondrocytes obtained from patients who underwent total knee arthroplasty were treated with p-OPN, OPN or buffer. Reverse transcription quantitative-polymerase chain reaction (RT-qPCR) and western blot analysis were used to assess the expression levels of proinflammatory factors, including interleukin (IL)-1β, tumor necrosis factor (TNF)-α, IL-6 and nuclear factor (NF)-κB. Apoptosis of human knee OA chondrocytes was detected by Annexin V-fluorescein isothiocyanate/propidium iodide flow cytometry. Compared with the controls, chondrocytes treated with OPN exhibited higher mRNA and protein expression levels of proinflammatory factors (IL-1β, TNF-α, IL-6 and NF-κB), and a higher percentage of apoptotic chondrocytes. Furthermore, chondrocytes treated with p-OPN exhibited the highest mRNA and protein expression levels of proinflammatory factors (IL-1β, TNF-α, IL-6, NF-κB) and the highest percentage of apoptotic chondrocytes. p-OPN induces chondrocyte apoptosis and proinflammatory factor release, which suggests that p-OPN may contribute to OA pathogenesis, and inhibition of p-OPN may provide a novel effective strategy to slow or halt OA progression. [ABSTRACT FROM AUTHOR]

Wnt inhibitory factor (WIF)-1 is a potent extracellular Wnt antagonist which may be used as a potential molecular therapy for the treatment of inflammatory and autoimmune diseases. Although previous studies have demonstrated that WIF-1 has a protective role in experimental studies of arthritis, its role in the various disease grades of osteoarthritis (OA) remains unclear. A total of 40 patients with various stages of primary OA of the knee and 10 control subjects were enrolled in the present study. Articular cartilage specimens were harvested from subjects following total knee arthroplasty or knee above amputation. Disease severity was determined according to Modified Mankin score and cartilage tissues were ascribed to four groups: Normal, mild, moderate and severe lesions. WIF-1 expression levels in articular cartilage were measured using immunohistochemical techniques. WIF-1 expression levels were detected in all cartilage tissues. As compared with the controls, patients with OA exhibited significantly decreased WIF-1 expression levels in the articular cartilage (0.19±0.05 vs. 0.26±0.04; P<0.01). Furthermore, articular cartilage WIF-1 expression levels in the moderate and severe lesion groups were significantly reduced, as compared with the controls (P<0.01) and mild lesion group (P<0.05). Subsequent analysis demonstrated that articular cartilage WIF-1 expression levels were negatively correlated with the severity of disease (r=-0.896, P<0.001). In conclusion, the results of the present study suggested that WIF-1 expression levels in articular cartilage may be negatively associated with progressive joint damage in patients with OA of the knee; therefore, WIF-1 expression may be a potential indictor for monitoring OA disease severity. [ABSTRACT FROM AUTHOR]

Previous studies have demonstrated that osteopontin (OPN) levels are elevated in the synovial fluid and articular cartilage, and are associated with the severity of knee osteoarthritis (OA). However, the role of OPN in the pathogenesis of OA has yet to be elucidated. The present study aimed to investigate the effects of OPN on the expression of the aggrecanases, a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)4 and ADAMTS5, in human OA chondrocytes, as they serve a key function in aggrecan degradation. Human OA chondrocytes were obtained from the knees of 16 patients with OA, and subsequently cultured in a monolayer. The chondrocytes were divided into three groups, which included the control (no treatment), N-OPN (treated with 100 ng/ml OPN, the normal circulating OPN concentration) and the H-OPN groups (treated with 1 μg/ml OPN, a high OPN concentration). Reverse transcription-quantitative polymerase chain reaction was performed to quantify the relative mRNA expression levels of ADAMTS4, ADAMTS5 and aggrecan in the chondrocytes. The mRNA expression levels of ADAMTS4 were significantly reduced in the N-OPN and H-OPN groups when compared with the control group (P<0.0001). In addition, the mRNA expression levels of ADAMTS4 were lower in the H-OPN group when compared with the N-OPN group (P<0.001). However, no statistically significant difference was observed in the relative mRNA expression levels of ADAMTS5 among the three groups (P>0.05). Furthermore, the mRNA expression levels of aggrecan were higher in the N-OPN and H-OPN groups when compared with the control group (P<0.0001), and a statistically significant difference was observed between the N-OPN and H-OPN groups with regard to the mRNA expression of aggrecan (P<0.0001). These results demonstrated that OPN may exert a protective effect in human OA chondrocytes against aggrecan degradation by suppressing the expression of ADAMTS4. [ABSTRACT FROM AUTHOR]

Background: The relationship between medial meniscus tear and posterior cruciate ligament (PCL) injury has not been exactly explained. We studied to investigate the biomechanical effect of partial and complete PCL transection on different parts of medial meniscus at different flexion angles under static loading conditions. Materials and Methods: Twelve fresh human cadaveric knee specimens were divided into four groups: PCL intact (PCL-I), anterolateral bundle transection (ALB-T), posteromedial bundle transection (PMB-T) and PCL complete transection (PCL-T) group. Strain on the anterior horn, body part and posterior horn of medial meniscus were measured under different axial compressive tibial loads (200-800 N) at 0°, 30°, 60° and 90° knee flexion in each groups respectively. Results: Compared with the PCL.I group, the PCL-T group had a higher strain on whole medial meniscus at 30°, 60° and 90° flexion in all loading conditions and at 0° flexion with 400, 600 and 800 N loads. In ALB-T group, strain on whole meniscus increased at 30°, 60° and 90° flexion under all loading conditions and at 0° flexion with 800 N only. PMB.T exihibited higher strain at 0° flexion with 400 N, 600 N and 800 N, while at 30° and 60° flexion with 800 N and at 90° flexion under all loading conditions. Conclusions: Partial PCL transection triggers strain concentration on medial meniscus and the effect is more pronounced with higher loading conditions at higher flexion angles. [ABSTRACT FROM AUTHOR]

Background: The clinical relationship between medial meniscus tear and anterior cruciate ligament (ACL) rupture has been well documented. However, the mechanism of this clinical phenomenon is not exactly explained. Our aim is to investigate the biomechanical impact of partial and complete ACL rupture on different parts of medial meniscus. Materials and Methods: Twelve fresh human cadaveric knee specimens were divided into four groups: ACL intact (ACL-I), anteromedial bundle transection (AMB-T), posterolateral bundle transection (PLB-T), and ACL complete transection (ACL-T) group. Strain on the anterior horn, body part, and posterior horn of medial meniscus were measured under 200 N axial compressive tibial load at 0°, 30°, 60°, and 90° of knee flexion, respectively. Results: Compared with the control group (ACL-I), the ACL-T group had a higher strain on whole medial meniscus at 0°, 60°, and 90° of flexion. But at 30°, it had a higher strain on posterior horn of meniscus only. As to PLB-T group, strain on whole meniscus increased at full extension, while strain increased on posterior horn at 30° and on body of meniscus at 60°. However, AMB-T only brought about higher strain at 60° of flexion on body and posterior horn of meniscus. Conclusions: Similar to complete rupture, partial rupture of ACL can also trigger strain concentration on medial meniscus, especially posterior horn, which may be a more critical reason for meniscus injury associated with chronic ACL deficiency. [ABSTRACT FROM AUTHOR]

Background: Epimedii herba is one of the most frequently used herbs in formulas that are prescribed for the treatment of osteoporosis in China and its main constituent is Epimedium pubescen flavonoid (EPF). However, it is unclear whether EPF during chronic exposure to cigarette smoke may have a protective influence on the skeleton.The present study investigated the effect of EPF on bone mineral status and bone turnover in a rat model of human relatively high exposure to cigarette smoke.Methods: Fifty male Wistar rats were randomized into five groups: controls, passive smoking groups and passive smoking rats administered EPF at three dosage levels (75, 150 or 300 mg/kg/day) in drinking water for 4 months.A rat model of passive smoking was prepared by breeding male rats in a cigarette-smoking box. Bone mineral content (BMC), bone mineral density (BMD), bone turnover markers, bone histomorphometric parameters and biomechanical properties were examined.Results: Smoke exposure decreased BMC and BMD, increased bone turnover (inhibited bone formation and stimulated its resorption), affected bone histomorphometry (increased trabecular separation and osteoclast surface per bone surface; decreased trabecular bone volume, trabecular thickness, trabecular number, cortical thickness, bone formation rate and osteoblast surface per bone surface), and reduced mechanical properties.EPF supplementation during cigarette smoke exposure prevented smoke-induced changes in bone mineral status and bone turnover.Conclusion: The results suggest that EPF can prevent the adverse effects of smoke exposure on bone by stimulating bone formation and inhibiting bone turnover and bone resorption. [ABSTRACT FROM AUTHOR]

Background: Many studies have identified smoking as a risk factor for osteoporosis, but it is unclear whether passive smoking has an effect on bone mineral density and bone turnover and if such an effect could cause osteoporosis.The purpose of the study was to investigate the effect of passive smoking on bone mineral density (BMD) and bone turnover and the relationship between BMD and bone turnover in female rat. Methods: Forty-eight female Wistar rats were randomized into six groups: 2-month, 3-month,4-month smokeexposed rats and their controls. A rat model of passive cigarette smoking was prepared by breeding female rats in a cigarette-smoking box for 2, 3 or 4 months. Serums were analyzed for levels of osteocalcin, bone-specific alkaline phosphatase (b-ALP) and Tartrate-resistant acid phosphatase 5b (TRACP 5b). BMD was assessed at lumbar vertebrae and femur by dual energy X-ray absorptiometry in passive smoking rats and in control rats. Results: BMD of lumbar spine and femur was lower in 4-month smoke-exposed female rats than that in controls. However, there was no significant difference in serum osteocalcin levels between smoke-exposed rats and controls. Significantly lower b-ALP and higher TRACP 5b were found in the 3-month or 4-month smoke-exposed rats compared to controls. Subsequent analysis showed that b-ALP positively correlated with BMD of the lumbar vertebrae(r = 0.764, P = 0.027) and femur(r = 0.899, P = 0.002) in 4-month smoke-exposed female rats. Furthermore, TRACP 5b levels negatively correlated with BMD of lumbar vertebrae (r = -0.871, P = 0.005) and femur (r = -0.715, P = 0.046) in 4-month smoke-exposed female rats. Conclusion: Our data suggest that smoke exposure can inhibit bone formation and increase bone resorption. The hazardous effects of passive smoking on bone status are associated with increased bone turnover in female rat. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "Viscosupplementation for Osteoarthritis of the Knee" by D. J. Hunter published in the March 12, 2015 issue of the "New England Journal of Medicine."

Abstract: Bipolar dislocation of the clavicle at acromioclavicular and sternoclavicular joint is an uncommon traumatic injury. The conservative treatments adopted in the past is associated with redislocation dysfunction and deformity. A 41 years old lady with bipolar dislocation of right shoulder is treated surgically by open reduction and internal fixation by oblique T-plate at sternoclavicular joint and Kirschner wire stabilization at acromioclavicular joint. The patient showed satisfactory recovery with full range of motion of the right shoulder and normal muscular strength. The case reported in view of rarity and at 2 years followup [ABSTRACT FROM AUTHOR]

Introduction: This study aimed to examine the associations of dietary magnesium (Mg) intake and serum Mg concentration with the high-sensitivity C-reactive protein (hsCRP) level in early radiographic knee osteoarthritis (OA) patients. Methods: Multivariable logistic regression was used to test the associations of dietary and serum Mg with the serum hsCRP in early radiographic knee OA patients after adjustment of a number of potential confounding factors. Results: A total of 936 early radiographic knee OA patients were included. A significant association between dietary Mg intake and hsCRP was observed. The multivariable-adjusted odds ratio (OR) (95% CI) for elevated hsCRP (3.0 mg/l) in the second, third, fourth, and fifth dietary Mg intake quintile were 0.44 (95% CI: 0.24-0.82), 0.58 (95% CI: 0.31-1.10), 0.34 (95% CI: 0.15-0.77), and 0.19 (95% CI: 0.06-0.57), respectively, compared with the lowest (first) quintile, and p for trend was 0.01. A significant association between serum Mg concentration and hsCRP was observed. The multivariable-adjusted OR (95% CI) for elevated hsCRP in the second, third, fourth, and fifth serum Mg concentration quintile were 0.63 (95% CI: 0.35-1.12), 0.83 (95% CI: 0.50-1.39), 0.53 (95% CI: 0.31-0.91), and 0.46 (95% CI: 0.25-0.85), respectively, compared with the lowest quintile, and p for trend was 0.01. Conclusion: The present study indicated that both dietary and serum Mg were inversely associated with serum hsCRP in early radiographic knee OA patients. [ABSTRACT FROM AUTHOR]

The aim of the present study was to investigate the in vitro effect of osteopontin (OPN) on the expression of hypoxia-inducible factor-2α (HIF-2α) in chondrocytes and the role of OPN in osteoarthritis (OA). Cartilage was purified from the tibial surfaces of patients with OA of the knee and cultured in vitro to obtain chondrocytes. Recombinant human OPN (rhOPN) and OPN small interfering RNA (siRNA) were used to treat the chondrocytes, and the changes in the expression levels of the HIF-2α gene were measured. An anti-CD44 blocking monoclonal antibody (mAb) was used to determine the probable ligand-receptor interactions. Reverse transcription-quantitative polymerase chain reaction assays were designed and validated with SYBR® Green dyes for the simultaneous quantification of the mRNA expression levels of OPN and HIF-2α. The mRNA expression level of HIF-2α was markedly decreased in the rhOPN-treated group compared with that in the control group; by contrast, OPN siRNA increased HIF-2α gene expression. CD44 blocking mAb suppressed the inhibitory effect of OPN on HIF-2α mRNA expression. The results of the present study suggest that OPN may play a protective role in OA by inhibiting HIF-2α gene expression in osteoarthritic chondrocytes through CD44 interaction. [ABSTRACT FROM AUTHOR]

Tissue inhibitors of metalloproteinases (TIMPs) regulate the activity of matrix metalloproteinases (MMPs) and enzymes from the a disintegrin and metalloproteinase domain with thrombospondin motifs family in osteoarthritis (OA). Elevated osteopontin (OPN) levels in plasma, synovial fluid and articular cartilage are associated with progressive OA joint damage; however, the role of OPN in the pathological changes of knee OA remains undetermined. The present study was undertaken to examine the effect of OPN on the expression of TIMP-1 and TIMP-2 mRNA in chondrocytes from 16 patients with knee OA. In this study, following the stimulation of human chondrocytes with recombinant human OPN (rhOPN; 100 ng/ml and 1 μg/ml, respectively) for 48 h, MTT assay was used to determine cell viability while the quantitative polymerase chain reaction (PCR) was used to detect the alterations in TIMP-1 and TIMP-2 levels. The results illustrated that neither 100 ng/ml nor 1 μg/ml rhOPN caused cytotoxicity or apoptosis of chondrocytes and that the relative mRNA expression of TIMP-1 and TIMP-2 was significantly increased in the 1 μg/ml rhOPN group compared with that in the control group (P=0.022 and P=0.003, respectively). However, no significant difference in expression was revealed between the 100 ng/ml rhOPN and control groups (P=0.998 and P=0.209, respectively). In conclusion, OPN may have a protective effect against pathological changes in advanced-stage OA. [ABSTRACT FROM AUTHOR]