Ubiquitin-specific protease 3 attenuates interleukin-1ß-mediated chondrocyte senescence by deacetylating forkhead box O-3 via sirtuin-3.

Osteoarthritis (OA) affects approximately 12% of the aging Western population. The sirtuin/forkhead box O (SIRT/FOXO) signaling pathway plays essential roles in various biological processes. Despite it has been demonstrated that ubiquitin-specific protease 3 (USP3) inhibits chondrocyte apoptosis induced by interleukin (IL)-1ß, the role of USP3/SIRT3/FOXO3 in the senescence of chondrocytes in OA is unclear. This study initially isolated articular chondrocytes and investigated the role of USP3 in IL-1ß-induced senescence of chondrocytes. After USP3 was overexpressed or silenced by lentivirus, expressions of genes and proteins were detected using quantitative polymerase chain reaction and immunoblotting, respectively. Cell cycle analysis was performed using flow cytometry. Reactive oxygen species (ROS) levels and senescence were analyzed. Then, SIRT3 was inhibited or overexpressed to explore the underlying mechanism. We found that overexpression of USP3 hindered IL-1ß-mediated cell cycle arrest, ROS generation, and chondrocyte senescence. The inhibition of SIRT3 blocked the protective effect of USP3 on cell senescence, whereas the overexpression of SIRT3 abolished USP3-silencing-induced cell senescence. Furthermore, SIRT3 attenuated cell senescence, probably by deacetylating FOXO3. USP3 upregulated SIRT3 to deacetylate FOXO3 and attenuated IL-1ß-induced chondrocyte senescence. This study demonstrated that USP3 probably attenuated IL-1ß-mediated chondrocyte senescence by deacetylating FOXO3 via SIRT3.

Downregulation of miR-223 and miR-19a induces differentiation and promotes recruitment of osteoclast cells in giant-cell tumor of the bone via the Runx2/TWIST-RANK/RANKL pathway.

Giant-cell tumor (GCT) of the bone is an invasiveness and high recurrent bone tumor that is considered borderline or potentially malignant. To explore the molecular mechanism leading to bone destruction and identify novel targets for treatment, we conducted silencing of miR-223 and miR-19a in stromal giant cells and identified TWIST and Runx2 as their target genes. We investigated the impact of these microRNAs and their target genes on stromal giant cells that promote the differentiation of monocyte/macrophages into osteoclast cells and recruitment to the bone microenvironment, which in turn enhances the bone destruction capacity of GCT. MiR-223 and miR-19a were found to regulate the expression of TWIST and Runx2, influence the RANKL-RANK pathway and the expression of MCP-1, and finally regulate the pathophysiological process of osteolytic bone destruction. Our results indicate that re-expression of miR-223 and miR-19a induces an inhibitory effect on the bone destruction capacity of GCT, suggesting that re-expression of miR-223 and miR-19a can be a novel strategy for the treatment of GCT.

Unusual cases of pigmented villonodular synovitis after arthroplasty.

Pigmented Villonodular Synovitis (PVNS) is a relatively rare, benign proliferation lesion of the synovium of large joints. The etiology is varied and unclear. We had report a 79-year-old woman had PVNS after 14 years right hip arthroplasty with metal prosthesis. Here we report another 4 patients had PVNS after arthroplasty. The second one had PVNS in the 2(th) year after hip arthroplasty with bone cement prosthesis. The specimen was brown and like usual PVNS in tissue. The third case had PVNS in the 8(th) after arthroplasty with human bone prosthesis because of the recurrence of PVNS. The proliferated synovium became black from brown. There was brown and many groups black pigment in the tissue. The fourth one had PVNS in the 4(th) year after knee arthroplasty with polyethylene prosthesis. The specimen was yellow. There was no pigment in the tissue but multinucleated giant cells with unstained foreign body. The fifth patient had PVNS in the 10(th) month after the left hip arthroplasty with metal prosthesis. The macroscopy was yellow. There were hemosiderin particles in the tissue but black metal particles. This indicates that arthroplasty with prosthesis could cause some new disease or PVNS had new etiology with different pathological show.

The effect of drainage tube on bleeding and prognosis after total knee arthroplasty: a prospective cohort study.

BACKGROUND: To evaluate the effect of drainage tube on prognosis after total knee arthroplasty (TKA) and explore an effective treatment with favorable prognosis. METHODS: In a prospective study, 18 patients with TKA for the first time were included and randomly divided into three groups, group A (no placement of drainage tube), group B (negative pressure drainage), and group C (4 h clamping drainage). Intraoperative and postoperative blood loss, operation time, and the drainage volume were recorded and analyzed. Arthrocele, ecchymosis, and range of motion (ROM) were examined postoperatively. The degree of pain was scored by Visual Analog Scale (VAS) after 6, 12, and 24 h of operation. The complications were examined and HSS (hospital for special surgery) knee score was taken during the follow-up period. RESULTS: There was no significant difference in operation time, total blood loss, intraoperative blood loss, and VAS score among three groups. Meanwhile, the hidden blood loss in group B was significantly decreased compared with group A (P = 0.0015). The postoperative drainage volume of group B was significantly increased compared with group C (P = 0.0002). No drainage increased the rate of arthrocele and ecchymosis. Compared with group A, ROM after 3 days of operation in groups B and C was significantly increased (P = 0.0357, P = 0.0372, respectively). During follow-up study, no deep infection or deep venous thrombosis was found. CONCLUSION: After TKA, early clamping of the drainage tube reduced the bleeding loss without adverse effect on prognosis, which might be useful for clinical application in future.

[Effect of extended release of posterior clearance on flexion clearence and range of motion of the knee in total knee arthroplasty].

OBJECTIVE: To observe the change of clearance and range of joint improved situation during total knee arthroplasty (TKA) by operating extended release manipulation of the posterior knee clearance. METHODS: A total of 120 patients with knee osteoarthritis undergoing unilateral TKA from March 2010 to March 2012 were equally randomized prospectively assigned to the experimental group and control group, each 60 cases. There were 46 male and 74 female patients, the mean age was 63.6 years (range from 49 to 75 years). After the osteotomy of the tibia and the femoral condyle and before the release of soft tissue intraoperation, patients in experimental group were taken the extended release manipulation of the posterior knee clearence while the control group were cleaned the osteophyte of the posterior condyle only, 2-sided paired t test was used to compare the clearence intraoperation and the time to flexion angle of 90° and 120° and the maximum angle after 3 months' follow-up. RESULTS: There was no significant difference of the index between the experimental group and control group (P > 0.05). Between experimental group and control group, the difference was significant in extention clearance ((18.9 ± 1.5) mm vs. (17.9 ± 1.6) mm, t = 3.53, P < 0.01) intraoperation, and no significant difference in flexion clearance ((20.7 ± 1.8) mm vs. (20.2 ± 1.9) mm, t = 1.48, P > 0.05). It took longer time for the knee flexion range of motion to 90°(t = 10.2399, P < 0.01) or 120°(t = 11.142, P < 0.01) of the control group than that of the experimental group, and the difference of the maximum range of motion between experimental group and control group was significant statistically at the 3-months follow-up (t = 4.4255, P < 0.01). All the patients were followed up for 3 - 24 months, average of 14.6 months, no femoral component loosening happened. CONCLUSIONS: Extended release of the posterior knee clearance benefits the knee extension clearence intraoperation and functional exercise of range of motion postoperation, while it is no meaning to the flexion clearence.

Patellar reshaping versus resurfacing in total knee arthroplasty - Results of a randomized prospective trial at a minimum of 7 years' follow-up.

OBJECTIVE: To compare the results of primary total knee arthroplasty with patellar reshaping or resurfacing. METHODS: One hundred thirty-three patients were randomized into patellar reshaping group and patellar resurfacing group. Patellar reshaping includes resecting the partial lateral facet of the patella and the osteophytes surrounding the patella, trimming the patella to match the trochlea of the femoral component. The minimum follow-up time was 7 years. The outcome was measured by anterior knee pain rate, Knee Society clinical score, and radiographs. RESULTS: Eight patients in the reshaping group (12.5%) and 10 patients in the resurfacing group (14.7%) complained of anterior knee pain (P=0.712). Meanwhile, there were no significant differences between the two groups in terms of total Knee Society score, Knee Society pain score, Knee Society function score, as well as anterior knee pain rate. CONCLUSIONS: With the numbers available, there was no significant difference between the groups treated with patellar reshaping or patellar resurfacing with regard to the KSS, anterior knee pain rate and radiographs. We prefer reshaping the patella to resurfacing the patella because the former preserves sufficient patellar bone stock and can easily be converted to patellar replacement if patients complain of recurrent anterior knee pain.

[The use of uncemented extensively porous-coated femoral components in the management of Vancouver type B2 periprosthetic femoral fractures].

OBJECTIVE: To assess the outcome of patients with Vancouver type B2 periprosthetic fractures treated with femoral revision using an uncemented extensively porous-coated implant. METHODS: From October 2002 to May 2007, a retrospective clinical and radiographic assessment of 10 patients with Vancouver type B2 periprosthetic fractures treated with femoral revision was evaluated, among which 4 was cement fixation, 6 was non-cement fixation in the index procedure. RESULTS: The mean follow-up for these patients was 44 months (range, 12 to 67 months). The mean Harris hip score was 87.6 points. All 10 reconstructions showed solid fracture union and a stable prosthesis, 8 was bone ingrowth, 2 was fibrous ingrowth. Complications in 4 patients included thigh pain in 1, stress shield in 3. CONCLUSIONS: Vancouver type B2 periprosthetic fractures treated with uncemented extensively porous-coated femoral stems incorporate distally allowing stable fixation.