A Retrospective Comparative Study of Endoscopic Treatment of Gastrocnemius Contracture using the Modified Soft Tissue Release Kit.

Background and Objectives: This study aimed to evaluate the effectiveness and safety of endoscopic gastrocnemius recession using the self-developed Modified Soft Tissue Release Kit. Materials and Methods: This retrospective review followed up 22 patients (34 feet) who underwent endoscopic surgery and 20 patients (30 feet) who received open surgery between January 2020 and January 2022. The American Orthopedic Foot and Ankle Society (AOFAS) ankle-hindfoot score and the maximum ankle dorsiflexion angle were evaluated preoperatively and at the last follow-up. Postoperative complications were recorded. Patient satisfaction was surveyed at the last follow-up. The comparison between quantitative data was analyzed with the Wilcoxon signed-rank test. The comparison between qualitative data was analyzed with the chi-square test. Results: There was no significant difference in the baseline characteristics between the two groups. The AOFAS score in the endoscopic group increased from 50 (18) points preoperatively to 90 (13) points at the last follow-up; the maximum ankle dorsiflexion angle increased from -7.7 (2.8) degrees to 10.6 (3.6) degrees. The AOFAS score in the open group improved from 47 (15) points preoperatively to 90 (18) points at the last follow-up; the maximum ankle dorsiflexion angle increased from -7.6 (4.0) degrees to 10.7 (3.3) degrees. The change values of the AOFAS scores in the endoscopic and open groups were 39 (15) and 40.5 (11) points, respectively, and there was no significant difference between them. The change values of the maximum ankle dorsiflexion angles in the endoscopic and open groups were 19.5 (4.3) and 19.1 (4.9) degrees, respectively, and there was no significant difference between them. There were no complications, such as sural nerve injury, in both groups. There was no significant difference between the two groups in satisfaction with the surgical outcome. Conclusions: Endoscopic gastrocnemius recession using the Modified Soft Tissue Release Kit can significantly improve the foot function with significant mid-term efficacy and high safety.

Three-dimensional printing-based personalized limb salvage and reconstruction treatment of pelvic tumors.

BACKGROUND AND OBJECTIVES: The treatment of pelvic tumors is widely recognized to be challenging. The purpose of this study was to evaluate the efficacy of personalized three-dimensional (3D) printing-based limb salvage and reconstruction treatment for pelvic tumors. METHODS: Twenty-eight pelvic tumor patients were enrolled. 3D printing lesion models and osteotomy templates were prepared for surgery planning, prosthesis design, and osteotomy assistance during surgery. 3D printing-based personalized pelvic prostheses were manufactured and used in all 28 patients. Follow-up of postoperative survival, prosthesis survival, imaging examinations, and Musculoskeletal Tumor Society (MSTS) lower limb functional scores were carried out. RESULTS: The mean follow-up period was 32.2 months, during which 16 patients had disease-free survival, 3 survived with the disease, and 9 died. The prostheses were stable, and the mean offset of the center of rotation was 5.48 mm. The prosthesis-bone interface showed good integration. For the 19 surviving patients, the mean MSTS lower limb functional score was 23.2. Postoperative complications included superficial infection in six patients and hip dislocation in three patients. CONCLUSIONS: Personalized 3D printing-based limb salvage and reconstruction was an effective treatment for pelvic tumors. Our patients achieved good early postoperative efficacy and functional recovery.

Association of Oral Behaviors with Anxiety, Depression, and Jaw Function in Patients with Temporomandibular Disorders in China: A Cross-Sectional Study.

BACKGROUND The aim of this study was to investigate the association of oral behaviors (OBs) with anxiety, depression, and jaw function in patients with temporomandibular disorders (TMDs) in China. MATERIAL AND METHODS A total of 537 patients diagnosed with TMD were included in this study (average age, 31.55±12.08 years; 86 men [16.0%] and 451 women [84.0%]). There were 31 cases of masticatory muscle pain, 459 cases of disc displacement, and 13 cases of arthralgia/arthrosis, and 34 cases were uncategorized. Patients were assessed using the Oral Behaviors Checklist (OBC), Jaw Functional Limitation Scale (JFLS), Generalized Anxiety Disorder-7 (GAD-7) scale, and Patient Health Questionnaire-9 (PHQ-9). The relationships between OBC scores and mouth opening, pain scores, JFLS, PHQ-9, and GAD-7 were evaluated with Spearman's correlation analysis. The median TMD symptom duration was 3 (0.5-154) months; men and women did not differ significantly in symptom duration or in the number of episodes of depression and anxiety. RESULTS The following OBs were common in patients with TMDs: "putting pressure on the jaw (52.9%)", "chewing food on 1 side (47.5%)", and "holding teeth together during activities other than eating (33.3%)". The OBC scores were significantly correlated with the JFLS, PHQ-9, and GAD-7 scores (P<0.01). CONCLUSIONS Patients with TMDs exhibit specific OBs, which are associated with depression, anxiety, and jaw function. It is necessary to further investigate the interaction of OBs with depression and anxiety in the development of TMDs.

3D-bioprinted gradient-structured scaffold generates anisotropic cartilage with vascularization by pore-size-dependent activation of HIF1α/FAK signaling axis.

Articular cartilage injury is one of the most common diseases in orthopedics, which seriously affects patients' life quality, the development of a biomimetic scaffold that mimics the multi-layered gradient structure of native cartilage is a new cartilage repair strategy. It has been shown that scaffold topography affects cell attachment, proliferation, and differentiation; the underlying molecular mechanism of cell-scaffold interaction is still unclear. In the present study, we construct an anisotropic gradient-structured cartilage scaffold by three-dimensional (3D) bioprinting, in which bone marrow stromal cell (BMSC)-laden anisotropic hydrogels micropatterns were used for heterogeneous chondrogenic differentiation and physically gradient synthetic poly (ε-caprolactone) (PCL) to impart mechanical strength. In vitro and in vivo, we demonstrated that gradient-structured cartilage scaffold displayed better cartilage repair effect. The heterogeneous cartilage tissue maturation and blood vessel ingrowth were mediated by a pore-size-dependent mechanism and HIF1α/FAK axis activation. In summary, our results provided a theoretical basis for employing 3D bioprinting gradient-structured constructs for anisotropic cartilage regeneration and revealed HIF1α/FAK axis as a crucial regulator for cell-material interactions, so as to provide a new perspective for cartilage regeneration and repair.

Validation of a Chinese version of the Jaw Functional Limitation Scale in relation to the diagnostic subgroup of temporomandibular disorders.

BACKGROUND: Oro-facial function is usually impaired by temporomandibular disorders (TMDs). Several studies on TMDs have used the Jaw Functional Limitation Scale (JFLS) to assess mandibular dysfunction. However, it was originally created in English and hence needs to be validated for use among Chinese people. OBJECTIVE: To develop a Chinese version of the JFLS for Chinese TMD patients and to investigate the validity and reliability of the scale. METHODS: Content validity and temporal stability were evaluated at two different occasions. The reliability and validity of the JFLS were tested in 483 TMD patients. Cronbach's alpha coefficient and split-half reliability were used to assess internal consistency, while the validity was evaluated by factor analysis. RESULTS: Three factors were extracted during exploratory factor analysis, accounting for 62.39% of the variance. The three-factor model was then measured using confirmatory factor analysis (χ2 /df = 3.6, root mean square error of approximation = 0.091, comparative fit index = 0.896). Internal (coefficient alpha values of .906 for all items and Guttman split-half reliability of 0.756) and test-retest (intra-class correlation coefficient = .851-.897, 95% confidence interval = 0.656-0.950) reliabilities were excellent. CONCLUSION: The Chinese version of the JFLS is reliable and valid for use in Chinese TMD patients.

Comparison and characterization of enriched mesenchymal stem cells obtained by the repeated filtration of autologous bone marrow through porous biomaterials.

BACKGROUND: When bone marrow is repeatedly filtered through porous material, the mesenchymal stem cells (MSCs) in the bone marrow can adhere to the outer and inner walls of the carrier material to become enriched locally, and this is a promising method for MSC enrichment. In this process, the enrichment efficiency of MSCs involved in the regulation of the cell ecology of postfiltration composites containing other bone marrow components is affected by many factors. This study compared the enrichment efficiency and characterized the phenotypes of enriched MSCs obtained by the filtration of autologous bone marrow through different porous bone substitutes. METHODS: Human bone marrow was filtered through representative porous materials, and different factors affecting MSC enrichment efficiency were evaluated. The soluble proteins and MSC phenotypes in the bone marrow before and after filtration were also compared. RESULTS: The enrichment efficiency of the MSCs found in gelatin sponges was 96.1% ± 3.4%, which was higher than that of MSCs found in allogeneic bone (72.5% ± 7.6%) and porous ß-TCP particles (61.4% ± 5.4%). A filtration frequency of 5-6 and a bone marrow/material volume ratio of 2 achieved the best enrichment efficiency for MSCs. A high-throughput antibody microarray indicated that the soluble proteins were mostly filtered out and remained in the flow through fluid, whereas a small number of proteins were abundantly (> 50%) enriched in the biomaterial. In terms of the phenotypic characteristics of the MSCs, including the cell aspect ratio, osteogenetic fate, specific antigens, gene expression profile, cell cycle stage, and apoptosis rate, no significant changes were found before or after filtration. CONCLUSION: When autologous bone marrow is rapidly filtered through porous bone substitutes, the optimal enrichment efficiency of MSCs can be attained by the rational selection of the type of carrier material, the bone marrow/carrier material volume ratio, and the filtration frequency. The enrichment of bone marrow MSCs occurs during filtration, during which the soluble proteins in the bone marrow are also absorbed to a certain extent. This filtration enrichment technique does not affect the phenotype of the MSCs and thus may provide a safe alternative method for MSC enrichment.

Relations between the Crowe classification and the 3D femoral head displacement in patients with developmental dysplasia of the hip.

BACKGROUND: The purpose of this study was to investigate the relationship between the three dimensional (3D) femoral head displacement in patients with developmental dysplasia of the hip (DDH) and Crowe classification. METHODS: Retrospectively, CT scans of 60 DDH patients and 55 healthy demography-matched healthy control subjects were analyzed. Using the anterior pelvic plane a pelvic anatomic coordinate system was established. The center coordinates of the femoral heads of both the DDH patients and control subjects were quantified relative to the pelvic coordinate system and were mapped proportionally to a representative normal pelvis for comparison. RESULTS: In the anteroposterior (AP) direction, the center of the femoral head was significantly more anterior in the DDH patients (type I, II, and III, respectively45.0 ± 5.5, 42.9 ± 7.1, and 43.9 ± 4.6 mm) when compared to the controls (50.0 ± 5.2 mm) (p < 0.001 for all). In the medial-lateral (ML) direction, the center of the femoral head was significantly more lateral in the DDH patients (type I, II, and III =103.5 ± 8.6, 101.5 ± 6.6, 102.1 ± 11.2 mm) when compared to the controls (87.5 ± 5.1 mm) (p < 0.001 for all). In the superior-inferior (SI) direction, the center of the femoral head was significantly more proximal in the DDH patients (type I, II, and III =62.4 ± 7.3, 50.0 ± 6.3, and 43.2 ± 6.6 mm) when compared to the controls (66.0 ± 6.2 mm) (p < 0.001 for all). CONCLUSIONS: The severity of DDH using the Crowe classification was related to the degree of the femoral head displacement in the SI direction, but not in the ML or AP directions. By assessing the 3D femoral head displacement in DDH patients, individualized component positioning might benefit surgical outcome.

Lenalidomide regulates osteocytes fate and related osteoclastogenesis via IL-1ß/NF-κB/RANKL signaling.

Osteolytic diseases are closely associated with osteocyte fate, indicating a more efficient and crucial role of osteocyte-targeting strategy in inhibiting osteoclastogenesis. Here, we investigated the effects of lenalidomide (Lena) on osteocyte fate in order to regulate osteoclastogenesis via effective cascade-controlling response. Our data revealed that lenalidomide treatment notably rescued IL-1ß induced loss of osteocyte viability by inhibiting osteocyte apoptosis with decreased osteoclast-related factors, RANKL and Sclerostin, as demonstrated by the restricted osteoclast formation and reduced bone resorption. Additionally, iTRAQ assay revealed that IL-1ß induced activation of NF-κB inhibitor α/ß were remarkably downregulated by lenalidomide, showing that lenalidomide impaired NF-κB signaling in osteocytes for inhibiting the expression of osteoclast specific genes in osteoclasts, which was further confirmed by KEGG pathway analysis and Western blot. More interestingly, the in vivo analysis of osteocyte apoptosis and osteoclastogenesis in osteoarthritis mice model indicated a role of lenalidomide in the regulation of osteocyte fate and the consequent inhibition of RANKL-induced osteoclastogenesis. Together, these results suggest that lenalidomide regulates osteocyte fate by attenuating IL-1ß/NF-κB signaling, thereby inhibiting RANKL expression for the attenuated osteoclastogenesis both in vitro and vivo, indicating a more efficient remedy among future anti-osteoclastogenesis approaches.

Mechanical stimulation promote the osteogenic differentiation of bone marrow stromal cells through epigenetic regulation of Sonic Hedgehog.

Mechanical unloading leads to bone loss and disuse osteoporosis partly due to impaired osteoblastogenesis of bone marrow stromal cells (BMSCs). However, the underlying molecular mechanisms of this phenomenon are not fully understood. In this study, we demonstrated that cyclic mechanical stretch (CMS) promotes osteoblastogenesis of BMSCs both in vivo and in vitro. Besides, we found that Hedgehog (Hh) signaling pathway was activated in this process. Inhibition of which by either knockdown of Sonic hedgehog (Shh) or treating BMSCs with Hh inhibitors attenuated the osteogenic effect of CMS on BMSCs, suggesting that Hh signaling pathway acts as an endogenous mediator of mechanical stimuli on BMSCs. Furthermore, we demonstrated that Shh expression level was regulated by DNA methylation mechanism. Chromatin Immunoprecipitation (ChIP) assay showed that DNA methyltransferase 3b (Dnmt3b) binds to Shh gene promoter, leading to DNA hypermethylation in mechanical unloading BMSCs. However, mechanical stimulation down-regulates the protein level of Dnmt3b, results in DNA demethylation and Shh expression. More importantly, we found that inhibition of Dnmt3b partly rescued bone loss in HU mice by mechanical unloading. Our results demonstrate, for the first time, that mechanical stimulation regulates osteoblastic genes expression via direct regulation of Dnmt3b, and the therapeutic inhibition of Dnmt3b may be an efficient strategy for enhancing bone formation under mechanical unloading.

Direct Leverage for Reducing the Femoral Head in Total Hip Arthroplasty Without Femoral Shortening Osteotomy for Crowe Type 3 to 4 Dysplasia of the Hip.

BACKGROUND: A number of methods for reduction in high hip dislocation in total hip arthroplasty (THA) are time-consuming and laborious, and require great surgical skills. This study aimed to introduce a new reduction technique to achieve rapid, safe, and easy reduction in high hip dislocation. METHODS: We retrospectively reviewed 74 THA patients (82 hips; 44 women, 30 men) with severe hip dysplasia who underwent direct leverage using a Hohmann retractor into the anatomical acetabulum without femoral shortening osteotomy between September 2007 and January 2014. Forty-nine hips were classified as Crowe III and 33 hips were classified as Crowe IV. The mean follow-up period was 5.1 years (range 2-8). RESULTS: Mean Harris Hip Score increased from 42.1 (range 24-71) before surgery to 89.9 (range 76-100) at final follow-up examination. The legs were lengthened by a mean of 3.0 cm (range 1.1-5.5) and 2.5 cm (range 1.1-3.5) in Crowe III hips and 3.6 cm (range 1.9-5.5) in Crowe IV hips postoperatively. The average leg-length discrepancy at the final follow-up examination was 0.4 cm (standard deviation 0.5 cm). One greater trochanteric fracture occurred during the hip reduction process. One patient developed femoral nerve palsies and recovered completely at 3 weeks postoperatively. CONCLUSION: Direct leverage using the Hohmann retractor for the reduction in high hip dislocation in THA without femoral shortening osteotomy is simple, safe, and effective.

Comparison of Total Hip Arthroplasty With and Without Femoral Shortening Osteotomy for Unilateral Mild to Moderate High Hip Dislocation.

BACKGROUND: This study compares the outcome between THA with and without femoral shortening osteotomy for unilateral mild to moderate high hip dislocation in developmental dysplasia of the hip patients. METHODS: The data on 42 hips in 42 patients who had undergone THA for unilateral mild to moderate high hip dislocation were retrospectively reviewed after being prospectively collected. In 22 patients, hips were reduced by soft tissue release and direct leverage using an elevator, without the osteotomy. The remaining 20 patients were treated with a subtrochanteric transverse shortening osteotomy. The mean follow-up of patients was 5 years (standard deviation = 1.0) for the nonosteotomy group and 6.2 years (standard deviation = 1.6) for the osteotomy group. RESULTS: The Harris Hip Score significantly improved in both groups. In the nonosteotomy group, we observed a lower leg length discrepancy compared with the osteotomy group (0.4 cm and 2.2 cm, respectively). Four patients (18.2%) in the nonosteotomy group and 15 patients (75%) in the osteotomy group developed a limp (P < .0001). Three patients (13%) developed femoral nerve palsy in the nonosteotomy group, but they all recovered completely within 6 months after the surgery. Nineteen patients in the nonosteotomy group showed knee valgus deformity immediately after the surgery but only 4 cases in the osteotomy group. CONCLUSION: Compared with THA with femoral shortening osteotomy, THA without the osteotomy was associated with a lower number of patients who developed a limp at the end of follow-up; however, the rehabilitation was slower and more difficult, and a larger number of patients showed reversible nerve palsy and knee valgus deformity.

In Vivo Identification and Induction of Articular Cartilage Stem Cells by Inhibiting NF-κB Signaling in Osteoarthritis.

Osteoarthritis (OA) is a highly prevalent and debilitating joint disorder characterized by the degeneration of articular cartilage. However, no effective medical therapy has been found yet for such condition. In this study, we directly confirmed the existence of articular cartilage stem cells (ACSCs) in vivo and in situ for the first time both in normal and OA articular cartilage, and explored their chondrogenesis in Interleukin-1ß (IL-1ß) induced inflammation environment and disclose whether the inhibition of NF-κB signaling can induce ACSCs activation thus improve the progression of experimental OA. We found an interesting phenomenon that ACSCs were activated and exhibited a transient proliferative response in early OA as an initial attempt for self-repair. During the in vitro mechanism study, we discovered IL-1ß can efficiently activate the NF-κB pathway and potently impair the responsiveness of ACSCs, whereas the NF-κB pathway inhibitor rescued the ACSCs chondrogenesis. The final in vivo experiments further confirmed ACSCs' activation were maintained by NF-κB pathway inhibitor, which induced cartilage regeneration, and protected articular cartilage from injury in an OA animal model. Our results provided in vivo evidence of the presence of ACSCs, and disclosed their action in the early OA stage and gradual quiet as OA process, presented a potential mechanism for both cartilage intrinsic repair and its final degradation, and demonstrated the feasibility of inducing endogenous adult tissue-specific mesenchymal stem cells for articular cartilage repair and OA therapy.

Custom Acetabular Cages Offer Stable Fixation and Improved Hip Scores for Revision THA With Severe Bone Defects.

BACKGROUND: Revision THA is particularly challenging in hips with severe acetabular bone loss. When the extent or geometry of the acetabular bone loss precludes more-straightforward techniques such as jumbo hemispheric cementless shells, reconstruction with morselized allograft protected by a custom cage may offer an alternative, but, to our knowledge, few series have reported on results with this approach. QUESTIONS/PURPOSES: For patients with severe (Paprosky IIIB) defects, we asked: do individualized custom cages result in (1) improved Harris hip scores; (2) restoration of hip center; and (3) a low incidence of surgical complications? METHODS: Twenty-six patients (26 hips) with a massive acetabular defect were involved in this study from 2003 to 2013. During this period, one patient was lost to followup and one died, leaving 24 patients (eight males, 16 females) in this retrospective analysis. The customized cages were individualized to each patient's bone defect based on rapid-prototype three-dimensional printed models. Mean followup was 67 months (range, 24-120 months). Harris hip scores were assessed before surgery and at each followup. Postoperative radiographs were evaluated for cage position, migration, and graft incorporation. Complications and reoperations were assessed by chart review. RESULTS: The mean Harris hip score improved from 36 (SD, 8; range, 20-49) to 82 (SD, 18; range, 60-96) (p < 0.001). Individualized custom cages resulted in generally reliable restoration of the hip center. No rerevisions have been performed. None of the cups showed radiographic migration, but one cage was believed to be loose, based on a circumferential 2-mm radiolucent line. Cancellous allografts appeared to be incorporated in 23 of 24 patients. One deep infection and one superficial infection were observed and treated with irrigation, débridement, and vacuum-sealing drainage. One dislocation and one suspected injury of the superior gluteal nerve also were observed and treated conservatively. CONCLUSIONS: Individualized custom cages using rapid prototyping and three-dimensional printing appeared to provide stable fixation and improved hip scores at short-term followup in this small, single-center series. As further improvements in the design and manufacturing process are made, future studies should evaluate larger patient groups for longer times, and, ideally, compare this approach with alternatives for these complex bone defects. LEVEL OF EVIDENCE: Level IV, therapeutic study.

A comparative, retrospective study of peri-articular and intra-articular injection of tranexamic acid for the management of postoperative blood loss after total knee arthroplasty.

BACKGROUND: Intra-articular injection of tranexamic acid (TXA) is known to be effective in controlling blood loss after total knee arthroplasty (TKA). However, this method has some disadvantages, such as TXA leakage due to soft tissue release. Peri-articular injection provides an alternative to intra-articular administration of TXA. This study aimed to evaluate the effects of peri-articular injection of TXA in reducing blood loss after TKA and compare them to those of intra-articular TXA injection. METHODS: This was a retrospective analysis of 127 patients who underwent primary, unilateral TKA for knee osteoarthritis in our hospital between January 2014 and December 2014. Cases were classified into 3 comparison groups: 49 patients in the peri-articular TXA group, 36 in the intra-articular group, and 42 in the control group (TXA not administered). Demographic variables, hemoglobin (Hb) measured before and after surgery, operation time, total amount of drained volume, time of removing drains, units of blood transfused peri- and postoperatively, estimated volume of blood loss, and preoperative comorbidities were retrieved from the patients' medical charts. Statistical analyses were performed using SPSS 19.0 software. RESULTS: There were no significant differences of demographic variables and operation time among three groups (P > 0.05). Compared to the control group, both TXA groups had a significantly reduced volume of blood loss, postoperative knee joint drainage, hemoglobin concentration, time of removing drains, and need for blood transfusion (P < 0.05). The effects of TXA were comparable for the two methods of injection (P > 0.05). There were no deep venous thrombosis or thromboembolic complications in any group. CONCLUSIONS: Peri-articular injection of TXA is as effective as an intra-articular injection in reducing postoperative blood loss during TKA. Both methods had a statistically significant benefit in reducing the change in Hb concentration, volume of joint drainage, and estimated volume of blood loss when compared to the control group. Peri-articular injection of TXA can significantly reduce the blood transfusion rate compared to the control group.

Nickel-Titanium Shape-Memory Sawtooth-Arm Embracing Clamp for Complex Femoral Revision Hip Arthroplasty.

PURPOSES: To examine the clinical outcomes of patients treated with a nickel-titanium shape-memory sawtooth-arm embracing clamp (Ni-Ti SSEC) in complex femoral revision surgery. METHODS: We retrospectively evaluated the outcomes for 21 complex femoral revision hip arthroplasties that we treated using an Ni-Ti SSEC. The Ni-Ti SSEC was used for various procedures, including the fixation of extremely long cortical windows (11 patients), femoral shaft osteotomy (4 patients), an extended trochanteric osteotomy (3 patients), and protection of a penetrated femoral cortex by a primary stem (3 patients). All patients received follow-up care for an average of 48.2 months. RESULTS: The mean time of Ni-Ti SSEC insertion intraoperatively was 6 minutes. The mean Harris Hip Score improved from 21.2 points before revision surgery to 83.1 points at the most recent examination. No implant failures or malunions occurred. Dislocation and deep infection occurred in 1 case during the follow-up period. CONCLUSIONS: Our results show that the embracing clamp is a simple and valid method for fixing osteotomies in treating complex femoral revision surgery.

Targeting Notch1 signaling pathway positively affects the sensitivity of osteosarcoma to cisplatin by regulating the expression and/or activity of Caspase family.

BACKGROUND: The introduction of cisplatin has improved the long-term survival rate in osteosarcoma patients. However, some patients are intrinsically resistant to cisplatin. This study reported that the activation of Notch1 is positively correlated with cisplatin sensitivity, evidenced by both clinical and in vitro data. RESULTS: In this study, a total 8 osteosarcoma specimens were enrolled and divided into two groups according to their cancer chemotherapeutic drugs sensitivity examination results. The relationship between Notch1 expression and cisplatin sensitivity of osteosarcoma patients was detected by immunohistochemistry and semi-quantitative analysis. Subsequently, two typical osteosarcoma cell lines, Saos-2 and MG63, were selected to study the changes of cisplatin sensitivity by up-regulating (NICD1 plasmid transfeciton) or decreasing (gamma-secretase complex inhibitor DAPT) the activation state of Notch1 signaling pathway. Our results showed a significant correlation between the expression of Notch1 and cisplatin sensitivity in patient specimens. In vitro, Saos-2 with higher expression of Notch1 had significantly better cisplatin sensitivity than MG63 whose Notch1 level was relatively lower. By targeting regulation in vitro, the cisplatin sensitivity of Saos-2 and MG63 had significantly increased after the activation of Notch1 signaling pathway, and vice versa. Further mechanism investigation revealed that activation/inhibition of Notch1 sensitized/desensitized cisplatin-induced apoptosis, which probably depended on the changes in the activity of Caspase family, including Caspase 3, Caspase 8 and Caspase 9 in these cells. CONCLUSIONS: Our data clearly demonstrated that Notch1 is critical for cisplatin sensitivity in osteosarcoma. It can be used as a molecular marker and regulator for cisplatin sensitivity in osteosarcoma patients.

Antibacterial properties of magnesium in vitro and in an in vivo model of implant-associated methicillin-resistant Staphylococcus aureus infection.

Periprosthetic infection remains a challenging clinical complication. We investigated the antibacterial properties of pure (99.9%) magnesium (Mg) in vitro and in an in vivo rat model of implant-related infection. Mg was highly effective against methicillin-resistant Staphylococcus aureus-induced osteomyelitis and improved new peri-implant bone formation. Bacterial icaA and agr RNAIII transcription levels were also assessed to characterize the mechanism underlying the antibacterial properties of the Mg implant.

Histone deacetylase1 promotes TGF-ß1-mediated early chondrogenesis through down-regulating canonical Wnt signaling.

Cartilage formation during both embryonic development and bone repairing processes involves mesenchymal stem cells (MSCs) differentiation. Wnt/ß-catenin signaling pathway inhibits early chondrogenesis and is down-regulated during Transforming growth factor-ß1 (TGF-ß1)-induced chondrogenesis. However, the regulatory molecules that participate in the process is unknown. This study was designed to investigate the underlying mechanisms that down-regulate Wnt/ß-catenin pathway during chondrogenesis. TGF-ß1-induced micromass cultures of C3H10T1/2 were used as chondrocyte differentiation model. Gene expression profile was detected by realtime-PCR. Regulatory role of HDAC1 on ß-catenin was investigated by luciferase assay, chromatin immunoprecipitation (ChIP) assay, co-immunoprecipitation (Co-IP) assay and in vitro ubiquitination assay. In this study, we showed that HDAC1 was induced and suppressed ß-catenin gene expression through direct binding to its promoter. Besides, HDAC1 could also interact with deacetylate ß-catenin protein through its deacetylase domain, which causes degradation of ß-catenin. Our results indicate that HDAC1 plays an important role in chondrogenesis and may represent a therapeutic target for modulation of cartilage development.

Dioscin inhibits osteoclast differentiation and bone resorption though down-regulating the Akt signaling cascades.

Bone resorption is the unique function of osteoclasts (OCs) and is critical for both bone homeostasis and pathologic bone diseases including osteoporosis, rheumatoid arthritis and tumor bone metastasis. Thus, searching for natural compounds that may suppress osteoclast formation and/or function is promising for the treatment of osteoclast-related diseases. In this study, we for the first time demonstrated that dioscin suppressed RANKL-mediated osteoclast differentiation and bone resorption in vitro in a dose-dependent manner. The suppressive effect of dioscin is supported by the reduced expression of osteoclast-specific markers. Further molecular analysis revealed that dioscin abrogated AKT phosphorylation, which subsequently impaired RANKL-induced nuclear factor-kappaB (NF-κB) signaling pathway and inhibited NFATc1 transcriptional activity. Moreover, in vivo studies further verified the bone protection activity of dioscin in osteolytic animal model. Together our data demonstrate that dioscin suppressed RANKL-induced osteoclast formation and function through Akt signaling cascades. Therefore, dioscin is a potential natural agent for the treatment of osteoclast-related diseases.