Stearoyl-CoA Desaturase-1 Attenuates the High Shear Force Damage Effect on Human MG63 Osteosarcoma Cells.

Mechanical regulation is known as an important regulator in cancer progression and malignancy. High shear force has been found to inhibit the cell cycle progression and result in cell death in various cancer cells. Stearoyl-CoA desaturase (SCD)-1, one of the important lipogenic enzymes, has recently been indicated as a potential pharmaceutical target in cancer therapy. In this study, we determined whether the cell fate control of shear force stimulation is through regulating the SCD-1 expression in cancer cells. Human MG63 osteosarcoma cells were used in this study. 2 and 20 dynes/cm2 shear forces were defined as low and high intensities, respectively. A SCD-1 upregulation in human MG63 osteosarcoma cells under 20, but not 2, dynes/cm2 shear force stimulation was shown, and this induction was regulated by Smad1/5 and peroxisome proliferator-activated receptor δ (PPARδ) signaling. Moreover, gene knockdown of PPARδ and SCD-1 in human MG63 osteosarcoma cells attenuated the differentiation inhibition and resulted in much more cell death of high shear force initiation. The present study finds a possible auto-protective role of SCD-1 upregulation in high shear force-damaged human MG63 osteosarcoma cells. However, its detailed regulation in the cancer fate decision of high shear force should be further examined.

Hyperglycemia inhibits osteoblastogenesis of rat bone marrow stromal cells via activation of the Notch2 signaling pathway.

Background: Bone fragility and related fractures are increasingly being recognized as an important diabetic complication. Mesenchymal progenitors often serve as an important source of bone formation and regeneration. In the present study, we have evaluated the effects of diabetes on osteoblastogenesis of mesenchymal progenitors. Methods: Primary bone marrow stromal cells (BMSCs) were isolated from control and streptozotocin-induced diabetic rats. These cells were evaluated for the effects of in vivo hyperglycemia on the survival and function of mesenchymal progenitors. We concomitantly investigated the effects of different concentrations of glucose, osmolality, and advanced glycation end product (AGE) on osteogenic differentiation and matrix mineralization of rat bone marrow mesenchymal stem cells (RMSC-bm). The relationship between the expression levels of Notch proteins and the corresponding ALP levels was also examined. Results: Our results revealed that in vivo hyperglycemia increased cell proliferation rate but decreased osteogenic differentiation and matrix mineralization of primary rat BMSCs. In vitro high glucose treatment, instead of high AGE treatment, induced a dose-dependent inhibition of osteoblastogenesis of RMSC-bm cells. Activation of the Notch2 signaling pathway, instead of the Notch1 or osmotic response pathways, was associated with these diabetic effects on osteoblastogenesis of mesenchymal progenitors. Conclusions: Hyperglycemia might inhibit osteoblastogenesis of mesenchymal progenitors via activation of the Notch2 signaling pathway.

The outcome of surgical management of proximal humeral fractures using locking plates: comparison between locking plates with different geometry.

BACKGROUND: Locking plate fixation appears to be a standard treatment for proximal humeral fracture. Different locking plate designs might result in different radiographic and functional outcomes. The original version of the Proximal Humeral Internal Locking System (PHILOS; DePuy Synthes, Warsaw, IN, USA) occupied the largest volume of the humeral head by screw distribution, whereas the Zimmer Periarticular Locking Plate (ZPLP) system (Zimmer Biomet, Warsaw, IN, USA) occupied the smallest. METHODS: We enrolled 50 patients undergoing ZPLP treatment and 50 undergoing PHILOS treatment. RESULTS: The postoperative amount of impaction was significantly higher using the ZPLP System than using the PHILOS. Subgroup analysis showed that medial calcar support was another critical factor that affected surgical outcomes, especially when using the ZPLP System. CONCLUSION: The amount of postoperative impaction was significantly higher when the ZPLP was used compared with the PHILOS locking plate. Medial calcar support is another critical factor that affects surgical outcomes. However, no significant differences in functional outcomes (Constant-Murley score) between the ZPLP System and the PHILOS were noted at the 12-month follow-up.

Treatment of displaced transverse fractures of the patella: modified tension band wiring technique with or without augmented circumferential cerclage wire fixation.

BACKGROUND: Displaced transverse fractures of the body of the patella are usually associated with disruption of extensor mechanism and should be fixed surgically. The most common method is a tension band wiring (TBW) technique. Some surgeons concurrently employ an augmented circumferential cerclage wiring (ACCW) technique to help fracture stabilization and aid in fracture healing; however, its role and effect on the treatment outcomes is unclear. METHODS: We performed a STROBE-compliant retrospective observational cohort study on all cases of acute closed patella fracture that were treated at our institution between 2006 and 2012. Of 185 episodes, 72 (38.9%) were eligible for this study according to our inclusion/exclusion criteria. We classified these subjects with AO/OTA type 34-C1.1 or 34-C2 lesions into two groups for analyses: fractures treated with modified TBW and ACCW (group 1, n = 27) and those treated with modified TBW alone (group 2, n = 45). Plain radiographs were used to evaluate radiographic outcomes and the effect of potential risk factors on fixation failure was analyzed by subgroup comparisons. RESULTS: Our results revealed that there were no significant differences in the rates of fixation failure (P = 0.620), nonunion (P = 0.620), and revision surgery (P = 0.620) between the groups. Although not statistically significant, there was a trend towards a positive risk association between fixation failure and age distribution > 60 years (10.0% vs. 0.0%, P = 0.124; OR = 8.0, P = 0.168) and > 70 years (9.4% vs. 2.5%, P = 0.321; OR = 4.0, P = 0.237) and the superficial level of the K-wires (12.0% vs. 1.5%, P = 0.117; OR = 6.3, P = 0.121). Regarding those modified TBW patients concurrently treated with an ACCW, the potential risk association between fixation failure and the superficial level of the K-wire was prone to increase further (28.6% vs. 0.0%, P = 0.060; OR = 18.6, P = 0.071). CONCLUSIONS: Concurrent application of an ACCW might be needless and not efficacious to help fracture stabilization and healing in patients having been treated with modified TBW for displaced transverse fractures of the body of the patella. Adherence to correct surgical technique such as putting the K-wires at the proper level and securing control of the both ends of the K-wires may be more important and help in improving outcomes.

Total knee arthroplasty in patients with Ranawat type-II valgus arthritic knee with a marked coronal femoral bowing deformity: comparison between computer-assisted surgery and intra-articular resection.

BACKGROUND: Proper limb and component alignments as well as soft tissue balance are vital for the longevity and optimal long-term outcomes of total knee arthroplasty (TKA). This procedure is technically demanding in patients with Ranawat type-II valgus arthritic knees with marked coronal femoral bowing. Computer-assisted surgery (CAS) and intra-articular bone resection with TKA are the treatments of choice for patients with ipsilateral extra-articular deformity. In theory, both CAS and intra-articular bone resection are beneficial in Ranawat type-II valgus arthritic knees with marked coronal femoral bowing deformity, but the literature on this topic is sparse. We compared the benefits of using these two techniques for TKA under this circumstance. METHODS: Patients who had Ranawat type-II valgus arthritic knees and marked coronal femoral bowing deformity and had undergone TKA at our hospital between 2005 and 2013 were enrolled in this retrospective study. Patients treated with CAS were assigned to the CAS-TKA group; patients treated with intra-articular bone resection were assigned to the Bone-Resect-TKA group. Radiographic parameters and clinical outcomes (International Knee Society (IKS) scores and patellar scores) in both groups were compared. RESULTS: Forty-seven patients (50 knees) met the inclusion criteria: 22 knees in the CAS-TKA group and 28 knees in the Bone-Resect-TKA group. Lateral retinaculum release was significantly (P = 0.008) higher in the Bone-Resect-TKA group. The joint-line was significantly properly restored in the CAS-TKA group (P = 0.011). The reconstructed mechanical axis was significantly (P = 0.012) closer to normal in the CAS-TKA group than in the Bone-Resect-TKA group. For component alignment, the femoral valgus and femoral flexion angles were significantly better in the CAS-TKA group (P = 0.002 and P = 0.006, respectively), but not the tibial valgus, tibial flexion, or patellar tilting angles. IKS scores and patellar scores were not significantly different between groups at a mean follow-up of 60.2 months. CONCLUSIONS: CAS-TKA was effective for obtaining proper alignment and joint-line restoration in patients with Ranawat type-II valgus arthritic knees and marked coronal femoral bowing deformity, but not for yielding better clinical outcomes. Additional large-scale prospective randomized cohort studies with long-term follow-ups are necessary to make evidence-based recommendations.