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.

Ideal intraarticular application dose of tranexamic acid in primary total knee arthroplasty: a prospective, randomized and controlled study.

BACKGROUND: Combined use of tranexamic acid (TXA) via intravenous (IV) and intraarticular (IA) routes is more effective in reducing blood loss than any single route in primary total knee arthroplasty (TKA), but the optimal dose of topical administration remains controversial. The aim of this study was to evaluate the efficacy and safety of different combined administration strategies and to determine an ideal IA application dose of TXA. METHODS: A total of 180 patients who underwent primary TKA were randomized to four groups (groups A/B/C/D) with the same single IV dose of 1 g TXA preoperatively and four different IA doses after wound closure: group A (0 g), group B (1 g), group C (2 g), and group D (4 g). The primary outcome measures included wound blood drainage, hemoglobin (Hb) concentration, and blood transfusion. The secondary outcome measures included wound complications, deep vein thrombosis (DVT) and symptomatic pulmonary embolism (PE). RESULTS: A total of 165 patients finished at least 3 months of follow-up visits. The amount of 48-hour blood drainage and calculated total blood loss in four groups decreased with the increased dose of TXA injected via IA route, and no difference was observed between groups C and D (P=0.6237 and P=0.9923, respectively). Hb was significantly higher in groups C and D than in groups A and B at postoperative day 1, 3 and 7, respectively (P<0.0001). Hb in group A was significantly lower than that in groups C and D at 1 month after surgery, whereas no intergroup difference was found in other groups. No intergroup difference was observed regarding DVT, PE or wound complications. CONCLUSIONS: The topical injection of 2 g TXA may have reached the "ceiling effect" of local use. A preoperative IV dose of 1 g TXA combined with an IA dose of 2 g TXA could be an optimal combination regimen.

The mineralization, drug release and in vivo bone defect repair properties of calcium phosphates/PLA modified tantalum scaffolds.

Calcium phosphate based biomaterials have been widely studied in biomedical areas. Herein, amorphous calcium phosphate (ACP) nanospheres and hydroxyapatite (HA) nanorods were separately prepared and used for coating tantalum (Ta) scaffolds with a polymer of polylactide (PLA). We have found that different crystal phases of calcium phosphate coated on Ta scaffolds displayed different effects on the surface morphologies, mineralization and bovine serum albumin (BSA) release. The ACP-PLA and HA-PLA coated on Ta scaffold were more favorable for in vitro mineralization than bare and PLA coated Ta scaffolds, and resulted in a highly hydrophilic surfaces. Meanwhile, the osteoblast-like cells (MG63) showed favorable properties of adhesion and spreading on both ACP-PLA and HA-PLA coated Ta scaffolds. The ACP-PLA and HA-PLA coated Ta scaffolds showed a high biocompatibility and potential applications for in vivo bone defect repair.

A New Insight of Kartogenin Induced the Mesenchymal Stem Cells (MSCs) Selectively Differentiate into Chondrocytes by Activating the Bone Morphogenetic Protein 7 (BMP-7)/Smad5 Pathway.

BACKGROUND Rotator cuff injury is the most common cause of shoulder disability, and although the repair technique has improved, the rate of rotator cuff reduction after repair is still high. The fibrocartilage region, which appears to be histologically inserted, cannot be regenerated. In recent years, studies have reported that mesenchymal stem cells (MSCs) have enhanced cartilage regeneration in the tendon and bone interface after rotator cuff repair, which has become a hot topic of research. MATERIAL AND METHODS Two mesenchymal stem cell types, SMSC (synovial-derived mesenchymal stem cells) and BMSC (bone marrow-derived mesenchymal stem cells) were intervened using kartogenin (KGN). The cytotoxicity was evaluated and the proliferation of the 2 cells was observed. Four commonly used cartilage phenotype genes were detected by quantitative real-time polymerase chain reaction, and the cartilage differentiation of MSCs induced by KGN was explored. The bidirectional regulation of the expression of BMP-7 and the downstream gene Smad5 was observed by constructing a lentiviral overexpression vector containing the target gene BMP-7. To explore whether BMP-7/Smad5 pathway activation promotes differentiation of SMSCs into chondrocytes. RESULTS KGN can induce the selective differentiation of endogenous MSCs into chondrocytes by activating the BMP-7/Smad5 pathway, which promotes the regeneration of interfacial cartilage, and improves the quality of tendon healing of the tendon after rotator cuff repair. CONCLUSIONS This study found a new biological intervention method to promote the effect of tendon on bone healing after rotator cuff repair.

Candida glabrata-Induced Refractory Infectious Arthritis: A Case Report and Literature Review.

The incidence of deep fungal infection due to non-albicans Candida species (especially Candida glabrata) has significantly increased in recent decades. Candida glabrata is an opportunistic pathogen of low virulence which mainly invades the gastrointestinal, genitourinary, and respiratory tracts, but has rarely been reported as complication of articular surgery in the literature. We present a case of knee fungal arthritis caused by C. glabrata after a minimally invasive arthroscopic surgery. In this case, the patient's knee got infected after arthroscopic treatment for a recurrent popliteal cyst, and she was unable to be cured by either debridement or antifungal drugs. Mycological and molecular identification of the necrotic tissues isolate revealed C. glabrata as etiologic agent. We originally planned to conduct a debridement once again, but it was found that the articular cartilage was extensively damaged during the operation. Besides, the magnetic resonance imaging of the affected knee also showed that the infection had invaded the subchondral bone. So we treated this case with a two-stage primary total knee arthroplasty with an antibiotic-laden cement spacer block. After a 10-month follow-up, the patient had completely recovered and has not experienced any recurrence to date. In addition, we review 21 cases of C. glabrata-induced infectious arthritis described to date in the literature.

Electrospinning of calcium phosphate-poly (d,l-lactic acid) nanofibers for sustained release of water-soluble drug and fast mineralization.

Calcium phosphate-based biomaterials have been well studied in biomedical fields due to their outstanding chemical and biological properties which are similar to the inorganic constituents in bone tissue. In this study, amorphous calcium phosphate (ACP) nanoparticles were prepared by a precipitation method, and used for preparation of ACP-poly(d,l-lactic acid) (ACP-PLA) nanofibers and water-soluble drug-containing ACP-PLA nanofibers by electrospinning. Promoting the encapsulation efficiency of water-soluble drugs in electrospun hydrophobic polymer nanofibers is a common problem due to the incompatibility between the water-soluble drug molecules and hydrophobic polymers solution. Herein, we used a native biomolecule of lecithin as a biocompatible surfactant to overcome this problem, and successfully prepared water-soluble drug-containing ACP-PLA nanofibers. The lecithin and ACP nanoparticles played important roles in stabilizing water-soluble drug in the electrospinning composite solution. The electrospun drug-containing ACP-PLA nanofibers exhibited fast mineralization in simulated body fluid. The ACP nanoparticles played the key role of seeds in the process of mineralization. Furthermore, the drug-containing ACP-PLA nanofibers exhibited sustained drug release which simultaneously occurred with the in situ mineralization in simulated body fluid. The osteoblast-like (MG63) cells with spreading filopodia were well observed on the as-prepared nanofibrous mats after culturing for 24 hours, indicating a high cytocompatibility. Due to the high biocompatibility, sustained drug release, and fast mineralization, the as-prepared composite nanofibers may have potential applications in water-soluble drug loading and release for tissue engineering.

Amorphous calcium phosphate, hydroxyapatite and poly(d,l-lactic acid) composite nanofibers: Electrospinning preparation, mineralization and in vivo bone defect repair.

Due to the outstanding bioactivity and biocompatibility, calcium phosphate (CaP) based materials have been widely investigated for applications in the biomedical fields. In this study, amorphous calcium phosphate (ACP) nanospheres and hydroxyapatite (HA) nanorods have been prepared and hybridized with poly(d,l-lactic acid) (PLA) to fabricate the composite nanofibers through electrospinning. The as-prepared ACP-PLA and HA-PLA composite nanofibers exhibit favorable mineralization behaviors in simulated body fluid (SBF). In the mineralization process, the ACP nanospheres and HA nanorods play an important role in the formation of HA nanosheets on the surface of composite nanofibers. The ACP-PLA and HA-PLA composite nanofibers show a high biocompatibility. The in vivo bone defect repair properties of the ACP-PLA and HA-PLA composite nanofibers are preliminarily investigated. The as-prepared ACP-PLA and HA-PLA composite nanofibers have promising applications in the biomedical fields.

Microwave-Assisted Hydrothermal Rapid Synthesis of Calcium Phosphates: Structural Control and Application in Protein Adsorption.

Synthetic calcium phosphate (CaP)-based materials have attracted much attention in the biomedical field. In this study, we have investigated the effect of pH values on CaP nanostructures prepared using a microwave-assisted hydrothermal method. The hierarchical nanosheet-assembled hydroxyapatite (HAP) nanostructure was prepared under weak acidic conditions (pH 5), while the HAP nanorod was prepared under neutral (pH 7) and weak alkali (pH 9) condition. However, when the pH value increases to 11, a mixed product of HAP nanorod and tri-calcium phosphate nanoparticle was obtained. The results indicated that the pH value of the initial reaction solution played an important role in the phase and structure of the CaP. Furthermore, the protein adsorption and release performance of the as-prepared CaP nanostructures were investigated by using hemoglobin (Hb) as a model protein. The sample that was prepared at pH = 11 and consisted of mixed morphologies of nanorods and nanoprisms showed a higher Hb protein adsorption capacity than the sample prepared at pH 5, which could be explained by its smaller size and dispersed structure. The results revealed the relatively high protein adsorption capacity of the as-prepared CaP nanostructures, which show promise for applications in various biomedical fields such as drug delivery and protein adsorption.

Amorphous calcium phosphate nanospheres/polylactide composite coated tantalum scaffold: facile preparation, fast biomineralization and subchondral bone defect repair application.

Calcium phosphate (CaP) materials are widely used in various biomedical areas such as drug/gene delivery and bone repair/tissue engineering. In this study, amorphous CaP nanospheres synthesized by a simple co-precipitation method are used to prepare the CaP-polylactide (CaP-PLA) composite. Then, the as-prepared CaP-PLA composite is used to coat tantalum (Ta) plates and porous scaffolds. Compared with bare Ta plate, CaP-PLA coated Ta plates show a high performance of surface biomineralization in simulated body fluid (SBF). In addition, the hydrophilicity of the CaP-PLA coated Ta plates is significantly improved. CaP-PLA coated Ta plates with bovine serum albumin (BSA) are prepared and used for the investigation of BSA release in vitro. The experimental results indicate a sustained BSA release property and simultaneous biomineralization of the as-prepared BSA-containing CaP-PLA coated Ta plates. Furthermore, CaP-PLA coated Ta scaffolds are favorable for the human osteoblast-like MG63 cells adhesion and spreading. The vascular endothelial growth factor (VEGF) and transforming growth factor (TGF)-containing CaP-PLA coated porous Ta scaffolds are used for the study of rabbit subchondral bone defect repair, covering with autogeneic periosteums. The as-prepared CaP-PLA composite coated Ta scaffolds are useful to guide the bone regeneration in vivo.

[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.

[The use of a pneumatic tourniquet in total knee arthroplasty: a prospective, randomized study].

OBJECTIVE: To determine the value of the use of a pneumatic tourniquet in total knee arthroplasty. METHODS: Sixty patients were prospectively randomized into 2 groups, one group underwent total knee replacement with a tourniquet (n = 30) and one without (n = 30). Operating time, blood loss, postoperative mean morphine requirement, swelling, ecchymosis, earlier straight-leg raising and postoperative knee flexion were measured in both groups. RESULTS: There was no significant difference in the total blood loss between the 2 groups although the intraoperative blood loss was significantly greater in those without a tourniquet. The mean morphine requirement, postoperative swelling, scope of ecchymosis, earlier straight-leg raising and postoperative knee flexion in the patients that had surgery without a tourniquet were significantly better than those with a tourniquet. CONCLUSION: Knee arthroplasty operation with the use of a tourniquet has only small benefits on the total blood loss, but hinder in patients' early postoperative rehabilitation exercises.

[Patella reshaping versus resurfacing in total knee arthroplasty: a prospective randomized study].

OBJECTIVE: To investigate the differences in the clinical outcome of total knee arthroplasty according to patellar reshaping or resurfacing. METHODS: From January 2002 to December 2002, 60 patients (60 knees) undergoing primary total knee arthroplasty for the treatment of osteoarthritis were enrolled in a prospective, randomized study. All patients received the same posterior-cruciate-substituting total knee prosthetic components. Patients were randomized to the treatment with reshaping or resurfacing of the patella, and the results were followed up for a mean of 54 months (40-60 months). Evaluations consisted of the determination of a Knee Society Score, range of motion for knees, patient satisfaction, and radiographs. RESULTS: With the numbers available for study, no significant difference was found between the knees that had patellar resurfacing and those that had patellar reshaping with regard to the overall score (P=0.12), the subscore for pain (P=0.90), and patient satisfaction (P=0.22). The results showed that the same prevalence of any anterior knee pain in two groups was 10%, and it did not represent a significant difference. The two groups showed statistical difference with regard to the total function score and range of motion. CONCLUSIONS: It has shown that total knee arthroplasty with patella reshaping or resurfacing dramatically relieves pain and improves the function. It seems that postoperative anterior knee pain is related either to the component design or to the details of the surgical technique, rather than to whether or not the patella is resurfaced.

[The use of a closed-suction drain in total knee arthroplasty: a prospective, randomized study].

OBJECTIVE: To determine the value of using a closed-suction drain in cemented knee arthroplasty. METHODS: One hundred patients were prospectively randomized into two groups, one group underwent cemented total knee replacement with a single deep closed-suction drain, and the other group (n = 50) no drain. RESULTS: The total blood loss was significantly greater in those with a drain although those without lost more blood into the dressings. There was no statistical difference in the postoperative swelling or pain score, ecchymosis, deep vein thromboses (DVT), time at which flexion was regained or the incidence of infection at a minimum of two years after surgery in the two groups. CONCLUSION: There is no evidence to support the use of a closed-suction drain in cemented knee arthroplasty.

Proximal humeral fractures treated with arthroplasty.

OBJECTIVE: To explore arthroplasty in treating 3- and 4-part fractures of the proximal humerus. METHODS: A total of 132 patients with proximal humeral fractures were treated in our hospital from July 1997 to February 2003. According to Neer's classification, the fractures of 45 patients (14 males and 31 females, aged 31-78 years, 56.1 years+/-7.8 years on an average) belonged to 3- or 4-part fractures (10 patients with 4-part fracture and 35 with 3-part comminuted fracture) and they were treated with shoulder joint arthroplasty. Unipolar prosthesis replacement of the head of humerus was made in 28 cases, while bipolar prosthesis replacement in 2 cases and total shoulder joint replacement in 15 cases. RESULTS: During the follow-up period (range: 12-72 months, mean: 37.3 months+/-4.1 months), among the 45 patients who suffered from fractures of the proximal humerus and underwent arthroplasty surgery, 44 patients (97.8%) had no postoperative pain and were satisfied with the active range of motion and with the whole treatment results. And radiography showed that the prostheses were at their good position. One patient had postoperative pain because he had so narrow medullary cavity that the humeral prosthesis could not be put deeply enough and the prosthesis head was a little higher over the anatomic level. He did not have good postoperative active range of motion, either. Then he received a review surgery and got satisfied results. Temporary shoulder stiffness was observed in one patient. Manual release of these adhesions improved the shoulder function. No evidence of nonunion of the fracture segments around the humeral prosthesis stem was found. CONCLUSIONS: Shoulder arthroplasty is a dependable method to restore the comfort and function of the shoulder joints of the patients with 3- or 4-part fractures of the proximal humerus.

The natural history of cervical disc calcification in children.

BACKGROUND: Calcification of cervical intervertebral discs is uncommon in children. The cases of approximately 200 children have been reported in the literature. The objective of the present study was to examine the natural history of this condition. METHODS: Seventeen consecutive children, ten boys and seven girls, with calcified cervical intervertebral discs were included in the study. The mean age at diagnosis was 7.7 years. Three children had had a fever, and two had a history of trauma. All of the children complained of neck pain except one who was asymptomatic and was identified by chance. On radiographs, the calcification was seen within the central part of the cervical intervertebral discs. All children had treatment of the symptoms, and they were then followed periodically until the disappearance of both the symptoms and the calcific deposits. RESULTS: The children were followed for a mean of five years, and all had a complete disappearance of both the symptoms and the calcification. None had recurrent symptoms or calcifications. The average time to resolution of the symptoms and the calcifications was 34.3 days (range, seventeen to 173 days) and fifteen months (range, three to sixty months), respectively. With the numbers available, factors such as age, level of disc calcification, severity of symptoms, and degree of spinal canal compromise were not related to the time of resolution. CONCLUSIONS: Cervical disc calcification in children is a self-limiting condition with an excellent prognosis. Even if clinical symptoms due to nerve-root or spinal cord compression are present, conservative therapy produces satisfactory results. Therefore, nerve-root or spinal cord compression by a calcified cervical disc should not be considered an absolute indication for surgical intervention.