Chinese Clinical Practice Guidelines in Treating Knee Osteoarthritis by Periarticular Knee Osteotomy.

Unicompartmental knee osteoarthritis (UKOA) is the early stage of knee joint degeneration, which is characterized by unicompartmental degeneration and mostly occurs in medial compartment. Pain and limited motion are main symptoms, which affect patients' life quality. Periarticular knee osteotomy (PKO) for lower extremity alignment correction is an effective treatment for UKOA with abnormal alignment, which could relieve pain and improve joint function by adjusting lower extremity alignment. At present, no clinical guidelines are available for the treatment of UKOA by PKO for lower extremity alignment correction. Experts from the Clinical New Technology Application Committee of the Chinese Hospital Association, Joint Surgery Study Group of the Chinese Orthopaedic Association of the Chinese Medical Association, and Osteoarthritis Study Group of the Chinese Association of Orthopaedic Surgeons of the Chinese Medical Doctor Association formulated these guidelines. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) grading system and the Reporting Items for Practice Guidelines in Healthcare (RIGHT) were adopted to select 25 most concerning questions. Finally, 25 recommendations were formulated through evidence retrieval, evidence quality evaluation, and the determination of directions and strength of recommendations. Recommendation items 1-5 are indications and contraindications for PKO for lower extremity alignment correction, items 6-21 are surgical methods and principles, item 22 describes 3D printing corrective osteotomy technique, and items 23-25 address the perioperative period, follow-up management, and other content. These guidelines are designed to improve the normalization and standardization of KOA treatment by PKO for lower extremity alignment correction.

RNA N6-methyladenosine demethylase FTO promotes osteoporosis through demethylating Runx2 mRNA and inhibiting osteogenic differentiation.

As a systemic disease, osteoporosis (OP) results in bone density loss and fracture risk, particularly in the hip and vertebrae. However, the underlying molecular mechanisms of OP development have not been fully illustrated. N6-Methyladenosine (m6A) is the most abundant modification of mRNAs, which is involved in many of pathological processes in aging disease. However, its role and regulatory mechanism in OP remains unknown. Here, we aimed to investigate the roles of m6A and its demethylase FTO in OP development. The results showed that m6A methylated RNA level was up-regulated in the bone marrow mesenchymal stem cells (BMSCs) from patients with OP. The level of N6-methyladenosine demethylase FTO was consistently decreased in the BMSCs from patients with OP. Functionally, lentivirus-mediated FTO overexpression in normal BMSCs to compromised osteogenic potential. Mechanism analysis further suggested that FTO overexpression decreased the m6A methylated and total level of runt related transcription factor 2 (Runx2) mRNA, subsequently inhibited osteogenic differentiation. We found that FTO inhibition could effectively improve the bone formation in ovariectomized osteoporotic mice in vivo. Together, these results reveal that RNA N6-methyladenosine demethylase FTO promotes osteoporosis through demethylating runx2 mRNA and inhibiting osteogenic differentiation.

Resveratrol prevents steroid-induced osteonecrosis of the femoral head via miR-146a modulation.

The purpose of this study was to investigate the possible use of resveratrol (Res) to reverse abnormal osteogenesis/osteoclastogenesis activity that occurs during femoral head osteonecrosis and to explore the detailed mechanisms. Application of Res to bone marrow-derived mesenchymal stem cells in vitro promoted survival, inhibited apoptosis, and downregulated expression of reactive oxygen species expression. Moreover, Res application was associated with elevated microRNA-146a (miR-146a) expression, osteogenic differentiation, and suppressed osteoclastic differentiation, which were markedly reversed by miR-146a inhibitor. Histopathological observations and micro-computed tomography scanning results indicated that the Res-treated group had lower incidence of osteonecrosis and better bone microstructure than the untreated group. Res inhibited osteoclastogenesis through altering the levels of sirtuin1 (Sirt1), nuclear transcription factor-κB (NF-κB), and receptor activator of NF-κB ligand (RANKL). Simultaneously, Res treatment improved bone formation and increased ß-catenin and runt-related transcription factor 2 (Runt2) expression levels, while reducing forkhead box class O (FOXO) family protein levels. The results of our study suggest that Res prevents steroid-induced osteonecrosis by upregulating miR-146a, and thereby stabilizes osteogenesis/osteoclastogenesis homeostasis via Wnt/FOXO and Sirt1/NF-κB pathways.

Identification of potential miRNA biomarkers for traumatic osteonecrosis of femoral head.

Traumatic osteonecrosis of femoral head (TONFH) is a common orthopedic disease caused by physical injury in hip. However, the unclear pathogenesis mechanism of TONFH and lacking of simple noninvasive early diagnosis method cause the necessity of hip replacement for most patients with TONFH. In this study, we aimed to identify circulating microRNAs (miRNAs) by integrated bioinformatics analyses as potential biomarker of TONFH. mRNA expression profiles were downloaded from the Gene Expression Omnibus database. Then we combined two miRNA screen methods: Weighted gene co-expression network analysis and fold change based differentially expressed miRNAs analysis. As a result, we identified 14 key miRNAs as potential biomarkers for TONFH. Besides, 302 target genes of these miRNAs were obtained and the miRNA-mRNA interaction network was constructed. Furthermore, the results of Kyoto Encyclopedia of Gene and Genome pathway analysis, Gene Ontology function analysis, protein-protein interaction (PPI) network analysis and PPI network module analysis showed close correlation between these 14 key miRNAs and TONFH. Then we established receiver operating characteristic curves and identified 6-miRNA signature with highly diagnosis value including miR-93-5p (area under the curve [AUC] = 0.93), miR-1324 (AUC = 0.92), miR-4666a-3p (AUC = 0.92), miR-5011-3p (AUC = 0.92), and miR-320a (AUC = 0.89), miR-185-5p (AUC = 0.89). Finally, the results of quantitative real-time polymerase chain reaction confirmed the significantly higher expression of miR-93-5p and miR-320a in the serum of patients with ONFH. These circulating miRNAs could serve as candidate early diagnosis markers and potential treatment targets of TONFH.

[Total arthroscopic internal drainage technique for the treatment of popliteal cyst].

OBJECTIVE: To compare the clinical effects of total arthroscopic internal drainage and arthroscopic combined with posterior small incision in the treatment of popliteal cyst. METHODS: From January 2015 to January 2017, 60 patients with popliteal cyst were treated, including 29 males and 31 females, aged 30 to 65(47.8±2.5) years old, with a course of disease (8.5±4.2) months. Among them, 30 cases received total arthroscopic internal drainage for popliteal fossa cyst(total arthroscopic group), 30 cases received arthroscopic combined with posterior small incision for popliteal fossa cyst(arthroscopic combined with small incision group). The operation time, intraoperative bleeding volume, incision length, Rauschning and Lindgren grade 0 recovery rate and Lysholm score were compared between the two groups. RESULTS: Twenty-nine patients in total arthroscopy group were followed up, and 28 patients in arthroscopy combined with small incision group were followed up for 8 to 20(12.8±2.1) months. Operation time: total arthroscopic group(45.32±5.71) min, arthroscopic combined small incision group (44.56±3.85) min; Rauschning and Lindgren grade 0 recovery: 23 cases in total arthroscopic group, 22 cases in arthroscopic combined small incision group; postoperative Lysholm score: total arthroscopic group 84.5±11.2, arthroscopic combined small incision group 83.2±12.7; there was no significant difference between the two groups(P>0.05). Intraoperative bleeding volume: total arthroscopic group(5.32±1.25) ml, arthroscopic combined small incision group(20.75±8.18) ml; incision length: total arthroscopic group (1.51±0.34) cm, arthroscopic combined small incision group (7.34±0.75) cm; the difference between the two groups was significant(P<0.05). At the last follow-up, the knee joint was examined by magnetic resonance imaging, and no recurrence of cyst was found. CONCLUSIONS: Total arthroscopic internal drainage and arthroscopic combined with posterior small incision technique for popliteal fossa cyst with intra-articular lesions have the same clinical effect, but less trauma and faster recovery.

Inhibition of microRNA-495 suppresses chondrocyte apoptosis through activation of the NF-κB signaling pathway by regulating CCL4 in osteoarthritis.

As a common form of arthritis, osteoarthritis (OA) represents a degenerative disease, characterized by articular cartilage damage and synovium inflammation. Recently, the role of various microRNAs (miRs) and their specific expression in OA has been highlighted. Therefore, the aim of the current study was to elucidate the role by which miR-495 and chemokine ligand 4 (CCL4) influence the development and progression of OA. OA mice models were established, after which the CCL4 and collagen levels as well as cell apoptosis were determined in cartilage tissue of OA mice. The chondrocytes of the OA mice models were subsequently treated with a series of miR-495 mimic, inhibitor, and siRNA against CCL4. Afterwards, miR-495 expressions as well as the levels of CCL4, p50, p65, and IkBa and the extent of IkBa phosphorylation in addition to the luciferase activity of NF-kB were measured accordingly. Finally, cell apoptosis and cell cycle distribution were detected. miR-495 was highly expressed while NF-κB, CCL4, and collagen II were poorly expressed. Cell apoptosis was elevated in the cartilage tissue of the OA mice. CCL4 was a potential target gene of miR-495. Downregulation of miR-495 led to accelerated chondrocyte proliferation accompanied by diminished cell apoptosis among the OA mice. Taken together, the results of the current study demonstrated that inhibition of miR-495 suppressed chondrocyte apoptosis and promoted its proliferation through activation of the NF-κB signaling pathway by up-regulation of CCL4 in OA.

Downregulation of long noncoding RNA LOC101928134 inhibits the synovial hyperplasia and cartilage destruction of osteoarthritis rats through the activation of the Janus kinase/signal transducers and activators of transcription signaling pathway by upregulating IFNA1.

Osteoarthritis (OA) is the most common disease of arthritis, a chronic joint disease that is always correlated with massive destruction such as cartilage destruction, inflammation of the synovial membrane, and so on. This study aims to explore the role of long noncoding RNA (lncRNA) LOC101928134 in the synovial hyperplasia and cartilage destruction, more specifically, in the Janus kinase/signal transducers and activators of transcription (JAK/STAT) signaling pathway in an OA rat model. Microarray-based gene expression analysis was conducted to screen out the lncRNA differentially expressed in OA and predict the target gene of the lncRNA with the involvement of the signaling pathway through Kyoto encyclopedia of genes and genomes (KEGG) analysis. A model of OA was established and treated with the small interfering RNA LOC101928134/inhibitor of JAK/STAT signaling pathway to investigate the relationship among LOC101928134, IFNA1, and the JAK/STAT signaling pathway in OA. The effect of LOC101928134 on the serum levels of IFNA1, interleukin-1ß, and tumor necrosis factor-α, and the apoptosis of synovial and cartilage cells was evaluated. LOC101928134, which was found to be highly expressed in knee joint synovial tissues of OA rats, regulated the expression of IFNA1 gene and inhibited JAK/STAT signaling pathway. Downregulation of LOC101928134 resulted in reduced knee joint synovitis, relived inflammatory damage, and knee joint cartilage damage of OA rats. Besides, synovial cell apoptosis was enhanced upon LOC101928134 downregulation, while cartilage cell apoptosis of OA rats was suppressed. These results demonstrate that downregulation of LOC101928134 suppresses the synovial hyperplasia and cartilage destruction of OA rats via activation of JAK/STAT signaling pathway by upregulating IFNA1, providing a new candidate for the treatment of OA.

Mesenchymal Stem Cells Induced by Microencapsulated Chondrocytes on Repairing of Intervertebral Disc Degeneration.

OBJECTIVE: To evaluate the therapeutic effects of mesenchymal stem cells induced by microencapsulated chondrocytes on repairing of intervertebral disc degeneration. METHODS: Rabbit chondrocytes and bone marrow-derived mesenchymal stem cells (MSC) were derived. Chondrocytes were microencapsulated by a microcapsule generator to produce microencapsulated chondrocytes (MEC). MSC were then co-cultured with MEC (MSC-MEC) and the properties and the therapeutic effects on repairing of intervertebral disc degeneration were studied. For the in vitro study, cell proliferation, type II collagen, and glycosaminoglycan (GAG) were studied. The MSC induced by chondrocytes in the Transwell system (MSC-MLC) and pure MSC were used as the control group. For the in vivo studied, MSC-MEC were implanted into the intervertebral disc degenerated (IDD) models, and the radiological images, biomechanical properties, collagen II, and histology of the discs were studied. The IDD, MSC, and MSC-MLC groups were used as the control group. RESULTS: In the in vitro study, no significant differences were found among the three groups, indicating that the microcapsule co-culture system will not affect the proliferation of MSC. The type II collagen quantity secreted by MSC-MEC was 23.57 ± 2.46 ng/µL, which was more than for MSC-MLC (15.14 ± 2.31 ng/µL) and MSC groups (4.17 ± 1.23 ng/µL, all P < 0.025). GAG secreted by MSC-MEC was 0.184 ± 0.006 mg/well, which was more than for the MSC-MLC (0.151 ± 0.011 mg/well) and MSC groups (0.023 ± 0.002 mg/well, all P < 0.025). In the in vivo study, no obvious degenerative or protrusive disc was found in the MSC-MEC group, while protrusive discs could be found in the MSC-MLC group, and both degenerative and protrusive discs were found in MSC and IDD groups, which indicated that the reparative effects of MSC-MEC on degenerated discs were better than for the control groups. Biomechanical properties of discs in the MSC-MEC group were maintained at all four time points (2nd, 4th, 8th, and 16th week after implantation). The compressive strength (CS) and the elastic modulus (EM) of MSC and IDD groups were consistently decreased. The CS of the MSC-MLC group was increased in the 4th week but decreased again in the 8th week, while the EM of the MSC-MLC group consistently decreased. Western blot results indicated that discs of the MSC-MEC group had more collagen II, which is an important component of discs. Histology staining showed that the nucleus pulposus of MSC-MEC was complete; no obvious fragment of component loss was found, while those of MSC-MLC, MSC, and IDD groups were widened, broken, and hollow. CONCLUSION: The microencapsulation method for half-contact co-culturing improves the differentiation extent of MSC, and MSC induced by chondrocytes could also be used for treatment of IDD.

Herbal Fufang Xian Ling Gu Bao prevents corticosteroid-induced osteonecrosis of the femoral head-A first multicentre, randomised, double-blind, placebo-controlled clinical trial.

BACKGROUND/OBJECTIVE: This is a multicentre, randomised, double-blind, placebo-controlled clinical trial to investigate the safety and efficacy of Chinese herbal Fufang Xian Ling Gu Bao (XLGB) with antiadipogenic compounds for the prevention of corticosteroid (CS)-induced osteonecrosis of femoral head (ONFH). METHODS: Patients of both genders, aged between 18 and 65 years, with diseases such as systemic lupus erythematosus, nephrosis, dermatosis and rheumatoid arthritis indicated for CS treatment and who did not show magnetic resonance imaging of ONFH at baseline were recruited into the study and then randomised into either XLGB group (n = 129) with daily oral administration of XLGB or placebo group (n = 146). RESULTS: Magnetic resonance imaging revealed a total of 30 ONFH cases at 6 months after CS treatment, with 6.98% (9 of 129 cases) and 14.4% (21 of 146 cases) in the XLGB group and placebo group, respectively, (p < 0.05), i.e., a 2-fold significantly less ONFH identified in the XLGB treatment group. Blood tests suggested that XLGB significantly inhibited the elevation of activated protein C resistance induced by CS treatment. CONCLUSION: This is the first multicentre clinical study to demonstrate that the antiadipogenic compounds-rich herbal Fufang (formula) XLGB is effective in preventing CS-associated ONFH in patients with immune-inflammatory diseases under CS treatment. THE TRANSLATIONAL POTENTIAL OF THIS ARTICLE: The translation potential of this clinical trial is that the initially officially approved clinical indication for XLGB for treatment of osteoporosis has been now also proven to be effective for a new clinical application.

Necrostatin-1 inhibits the cell death of osteoblasts induced by glucocorticoid.

Glucocorticoids have been shown to induce apoptosis in different cell types. Recent studies have indicated that apoptosis may not be the only form of death that is activated in osteoblasts in response to glucocorticoids. The aim of this study was to investigate whether necrostatin-1 could protect osteoblasts from glucocorticoid-induced cell death. Dexamethasone could induce both apoptotic and necrotic cell death in MC3T3-E1 cells, in a dose- and time-dependent manner. Necrotic cell death was induced by dexamethasone in MC3T3-E1 cells and was characterized by caspase independence, delayed externalization of phosphatidylserine, cellular swelling and plasma membrane disruption. Blockages of necroptotic induction by a special inhibitor (Necrostatin-1) succeed to protect cells against dexamethasone induced cell death. The levels of RIP-1 production and loss of mitochondrial membrane potential were also determined to assess the effects of dexamethasone. This study showed, for the first time, that high-doses of dexamethasone can induce necrotic-like cell death in osteoblastic MC3T3-E1 cells, and this induction could be inhibited by necrostatin-1.

HSYA alleviates secondary neuronal death through attenuating oxidative stress, inflammatory response, and neural apoptosis in SD rat spinal cord compression injury.

BACKGROUND: Hydroxysafflor yellow A (HSYA) is a major active component of yellow pigment extracted from safflowers; this compound possesses potent neuroprotective effects both in vitro and in vivo. However, underlying mechanism of HSYA is not fully elucidated. The present study investigated the protective effects of HSYA in rat spinal cord compression injury model and related mechanisms involved. METHODS: Sprague-Dawley rats were divided as Sham, Control, and HSYA groups (n = 30 per group). Spinal cord injury (SCI) model was induced by application of vascular clips (force of 50 g, 1 min) to the dura at T9-T10 level of vertebra. Injured animals were administered with either HSYA (8 mg/kg at 1 and 6 h after injury, then 14 mg/kg, for a total of 7 days at 24-h time intervals) or equal volume of saline by intraperitoneal injection. RESULTS: From this experiment, we discovered that SCI in rats resulted in severe trauma, which is characterized by tissue damage, lipid peroxidation, neutrophil infiltration, inflammation mediator release, and neuronal apoptosis. However, HSYA treatment significantly reduced the following: (1) degree of tissue injury (histological score) and edema; (2) neutrophil infiltration (myeloperoxidase activity); (3) oxidative stress (superoxide dismutase, malondialdehyde, and nitric oxide); (4) pro-inflammatory cytokine expression (tumor necrosis factor-α, interleukin-6, inducible nitric oxide synthase, cyclooxygenase-2); (5) nuclear factor-κB activation; (6) apoptosis (terminal deoxynucleotidyl transferase dUTP nick end labeling staining and cysteine-aspartic protease-3 activity). Moreover, in a separate set of experiments, we clearly demonstrated that HSYA treatment significantly ameliorated recovery of limb function (as evaluated by Basso, Beattie, and Bresnahan behavioral recovery scores). CONCLUSIONS: Treatment with HSYA restrains development of oxidative stress, inflammation response, and apoptotic events associated with SCI of rats, demonstrating that HSYA is a potential neuroprotectant for human SCI therapy.

Patient-specific core decompression surgery for early-stage ischemic necrosis of the femoral head.

INTRODUCTION: Core decompression is an efficient treatment for early stage ischemic necrosis of the femoral head. In conventional procedures, the pre-operative X-ray only shows one plane of the ischemic area, which often results in inaccurate drilling. This paper introduces a new method that uses computer-assisted technology and rapid prototyping to enhance drilling accuracy during core decompression surgeries and presents a validation study of cadaveric tests. METHODS: Twelve cadaveric human femurs were used to simulate early-stage ischemic necrosis. The core decompression target at the anterolateral femoral head was simulated using an embedded glass ball (target). Three positioning Kirschner wires were drilled into the top and bottom of the large rotor. The specimen was then subjected to computed tomography (CT). A CT image of the specimen was imported into the Mimics software to construct a three-dimensional model including the target. The best core decompression channel was then designed using the 3D model. A navigational template for the specimen was designed using the Pro/E software and manufactured by rapid prototyping technology to guide the drilling channel. The specimen-specific navigation template was installed on the specimen using positioning Kirschner wires. Drilling was performed using a guide needle through the guiding hole on the templates. The distance between the end point of the guide needle and the target was measured to validate the patient-specific surgical accuracy. RESULTS: The average distance between the tip of the guide needle drilled through the guiding template and the target was 1.92±0.071 mm. CONCLUSIONS: Core decompression using a computer-rapid prototyping template is a reliable and accurate technique that could provide a new method of precision decompression for early-stage ischemic necrosis.

[Subtype classification of Garden III femoral neck fractures in the elderly based on frontal Garden index and its clinical significance].

OBJECTIVE: To retrospectively study postoperative Garden III femoral neck fractures in the elderly so as to explore the different degree of displacement of Garden III femoral neck fracture, and discuss the basis and clinical significance of the subtype classification. METHODS: A total of 492 patients with complete clinical data out of the 1397 patients with femoral neck fractures treated by closed reduction and internal fixation with cannulated compression screws from September 2005 to September 2010 were included in the study. Each patient's frontal Garden Index was measured. On the basis of the frontal Garden Index, these cases were divided into three types:type A, which frontal Garden Index was more than or equal to 140°, included 53 males and 84 females with an average age of(65.3±7.2) years old ranging from 60 to 75 years old; type B, more than 120°and less than 140°, included 79 males and 172 females with an average age of (67.5±3.6) years old;and type C, less than or equal to 120°, included 38 males and 66 with an average age of(68.6±5.7) years old. Aspects were followed up including complications, consequences and hip joint function. The fracture healing and femoral head necrosis were compared among three types. RESULTS: Operative incision of 492 cases was primary healing, and no infection and other complications occurred. All patients were followed up from 2 to 10 years with an average of 6.3 years, the healing of femoral neck fracture occurred in 432 cases, and the total union rate was 87.8%. Femoral head necrosis occurred in 83 cases, and the total necrosis rate of femoral head was 16.9%. The nonunion rate of type A was 6.6%, type B was 13.5%, and type C was 16.3%, there were significant differences among three types(χ²2AB=4.377, P=0.036;χ²2AC=5.872, P=0.015;χ²2BC=0.469, PBC=0.494). The necrosis rate of femoral head of group A was 8.8%, group B was 16.7%, and group C was 27.9%, there were significant differences among three groups(χ²2AB=4.704, P=0.030;χ²2AC=15.317, P=0.000;χ²2BC=5.715, P=0.017). CONCLUSIONS: It is different for the degree of displacement of Garden III femoral neck fracture in the elderly. Based on frontal Garden Index to differentiate degree of fracture displacement, Garden III femoral neck fracture would be divided into A, B and C subtypes. The prognosis of Garden III femoral neck fracture in the elderly is negatively related to its degree of displacement, which has clinical significance to make treatment plan for Garden III femoral neck fracture in the elderly.

[Proximal femoral geometry changes after femoral neck fracture treated with total hip arthroplasty].

OBJECTIVE: To observe the changes of proximal femoral geometry after femoral neck fracture treated with THA, analyze the existent of differences and their manifestation. METHODS: All patients of femoral neck fracture (FNF) and osteonecrosis of femoral head (ONFH) were treated with THA by the same operating team from January to December of 2014, including 22 patients with FNF (11 males and 11 females,with age from 44 to 83 years old (means 66.18 ± 11.47) and 23 patients with ONFH (12 males and 11 females, with age from 19 to 68 years old (means 51.91 ± 11.76). After THA, height of femorals, offsets, osteotomy position and adjusting modes were measured and the statistic analysis was done. RESULTS: After THA, all patients were measured. Decreased femoral height, offsets and lower osteotomy positions were found in patients with FNF than those with ONFH, and 3 kinds of adjustments because of lower-positional osteotomy were found. CONCLUSION: After THA, lower-positional osteotomy and decreased femoral offsets may occur on patients with FNF. The adjustments caused by lower-positional osteotomy may lead to negative results.

Apoptosis associated with Wnt/ß-catenin pathway leads to steroid-induced avascular necrosis of femoral head.

BACKGROUND: The objective of the current study was to establish a rat model to investigate apoptosis in steroid-induced femoral head osteonecrosis occurring via the Wnt/ß-catenin pathway. METHODS: Male Sprague-Dawley (SD) rats were randomly divided into a control group (group A), model group (group B) and sFRP1 group (group C), each consisting of 24 rats, and the rats were intravenously injected with LPS (10 µg/kg body weight). After 24 h, three injections of MPS (20 mg/kg body weight) were administered intramuscularly at 24-h intervals. The rats in group C were injected intramuscularly with 1 µg/kg sFRP1 protein per day for 30 days, beginning at the time of the first MPS administration. The group A rats were fed and housed under identical conditions but received saline injection. All animals were sacrificed at weeks 2, 4 and 8 from the first MPS injection. Histopathological staining was preformed to evaluated osteonecrosis. Apoptosis was detected via quantitative terminal deoxynucleotidyl transferase (TdT) deoxyuridine triphosphate nick-end labelling (TUNEL) staining, caspase-3 activity assay, and detection of Bcl-2 and Bax protein expression by immunohistochemistry and Western blotting. Wnt/ß-catenin pathway signalling molecules, including activated ß-catenin and c-Myc, were detected by immunohistochemistry and Western blotting. RESULTS: Typical osteonecrosis was observed in groups B and C. Apoptosis gradually increased with increasing time in both groups B and C. More severe osteonecrosis and apoptosis were observed in group C compared with group B. The expression levels of caspase-3 and Bax were higher while that of Bcl-2 was lower in group C compared with group B. The expression levels of activated ß-catenin and c-Myc gradually decreased with increasing time in both groups B and C, and they were lower in group C compared with group B. CONCLUSIONS: The Wnt/ß-catenin pathway is involved in the pathogenesis of early stage SANFH, as we have demonstrated in an SANFH rat model, and it may act through the regulation of c-Myc, which affects the cell cycle and cell apoptosis.

[Comparative study of less invasive stabilization system (LISS) and the condylar support plates for the treatment of AO type C distal femoral fractures in adults].

OBJECTIVE: To summarize the complications and the early clinical effect of less invasive stabilization system and the femoral condylar support plates in the treatment of AO type C distal femoral fractures. METHODS: From September 2007 to February 2012, 46 patients with AO type C distal femoral fractures were retrospectively studied. Of all patients 25 were treated with less invasive stabilization system including 14 males and 11 females with a mean age of (56.3±4.2) years old; according to AO classification, there were 14 cases of C1, 8 cases of C2 and 3 cases of C3 with a mean hospital stay of (15.6±1.7) days. While 21 cases were treated with femoral condylar support plates fixation including 12 males and 9 females with a mean age of (53.8±5.1) years old;there were 13 cases of C1, 6 cases of C2 and 2 cases of C3 with a mean hospital stay of (17.8±2.2) days. Comparative analysis was performed from the operation related index,postoperative complications and Evanich score of the knee joint function between the two groups at follow-up. RESULTS: All 46 patients were followed up from 13 to 38 months with a mean time of 19.6 months after surgery. Complications included 1 case with infection,3 cases with internal fixation failure, 1 case with nonunion and 1 case with activity limitation of the affected knee. The differences in the incision length, blood loss, fracture healing time were significant between two groups (P<0.05), while there was no significant difference in the duration of operations, hospital stays and the incidence of postoperative complications between two groups (P>0.05). The statistical significance was also found in the Evanich score at last follow-up between two groups (P<0.05). CONCLUSION: Patients with less invasive stabilization system fixation had the characteristics of less trauma, shorter fracture healing time and better functional recovery. Less invasive stabilization system had became one of the ideal internal fixations in the treatment of AO type C distal femoral fractures.

Repair effect of coexpression of the hVEGF and hBMP genes via an adeno-associated virus vector in a rabbit model of early steroid-induced avascular necrosis of the femoral head.

We investigated the repair effect of coexpression of the human vascular endothelial growth factor (hVEGF) and human bone morphogenetic protein (hBMP) genes via an adeno-associated virus (AAV) vector in a rabbit model of early steroid-induced avascular necrosis of the femoral head (SANFH). The following AAV vectors were constructed: AAV-green fluorescent protein, AAV-VEGF, AAV-BMP, and AAV-VEGF/BMP. The rabbit model was induced using lipopolysaccharide and methylprednisolone. Virus vector was injected into the core decompression region at a dose of 25 µL per side after core decompression operation in each group. hVEGF165 and BMP-7 expressions were determined by Western blotting and immunohistochemical staining, and the femoral head was examined by magnetic resonance image scan, histopathologic staining, ink vessel staining, microcomputed tomography scan, and biomechanical assessment to determine the repair effect. The vector AAV-VEGF/BMP successfully expressed hVEGF165 and BMP-7 at the gene and protein levels at 12 weeks after virus injection. The expression of hVEGF165 promoted metabolism of the necrotic region by inducing vessel formation. The expression of BMP-7 promoted osteogenesis by increasing the mineral density and biomechanical strength of the femoral head. The repair effect of the AAV-VEGF/BMP group was better than those of the AAV-VEGF and AAV-BMP groups in the rabbit early SANFH model. The AAV-VEGF/BMP vector improved the bone repair capacity of the necrotic femoral head by inducing angiogenesis and improving bone quality in the femoral head.

Association of toll-like receptor 4 signaling pathway with steroid-induced femoral head osteonecrosis in rats.

Osteonecrosis of the femoral head is frequently observed in patients treated with excessive corticosteroids. However, the pathogenesis of corticosteroid-induced osteonecrosis remains unclear. The purpose of this study was to investigate the role of Toll-like receptor 4 (TLR4) signaling pathway in steroid-induced femoral head osteonecrosis in rats. Male Sprague-Dawley rats were injected intramuscularly with 20 mg/kg methylprednisolone (MP) for 8 weeks, twice per week. The animals were sacrificed at 2, 4 and 8 weeks after the last MP injection, respectively, and then allocated to the 2-, 4- and 8-week model groups (n=24 each). Rats in the control group (n=12) were not given any treatment. Histopathological analysis was performed and the concentration of tartrate-resistant acid phosphatase (TRAP) in plasma was determined. The activation of osteoclasts in the femoral head was assessed by TRAP staining. The expression of TLR4, MyD88, TRAF6 and NF-κB p65 that are involved in TLR4 signaling, and MCP-1 production were detected by using real-time PCR (RT-PCR) and Western blotting. The results showed that the osteonecrosis in the femoral head was clearly observed and the concentration of TRAP in the plasma was increased in the model rats. The femoral head tissues in MP-treated rats were positive for TRAP and the intensity of TRAP staining was greater in MP-treated rats than in control rats. As compared with the control group, the mRNA expression of TLR4 signaling-related factors was enhanced significantly at 4 and 8 weeks, and the protein levels of these factors increased significantly with time. It was concluded that MP could induce the femoral head osteonecrosis in rats, which was associated with osteoclast activation via the TLR4 signaling pathway. These findings suggest that TLR4 signaling pathway plays a pivotal role in the pathogenesis of steroid-induced osteonecrosis.

Partial greater trochanter osteotomy for hip reduction in total hip arthroplasty for high dislocated hip: a preliminary report.

BACKGROUND: Hip reduction in total hip arthroplasty for high dislocated hips is difficult. Various femur osteotomy procedures have been used for hip reduction, but these methods increase operative time and risk of nonunion. We investigated the efficacy of a novel partial greater trochanter osteotomy technique for hip reduction in total hip arthroplasty for patients with high hip dislocation. METHODS: Twenty-one patients (23 hips) with high dislocated hip were treated with total hip arthroplasty that included partial greater trochanter osteotomy, i.e., the upper 2/3 greater trochanter was resected, and the gluteus medius muscle attachment was spared. The clinical outcome was evaluated by comparing the Harris hip scores and radiographic exam results, obtained before surgery and at follow-ups. RESULTS: Follow-ups of 21 patients ranged from 13 to 56 months. The mean Harris hip score increased from preoperative 55.0 (36-69) to postoperative 86.1 (71-93; P = 0.00). The average preoperative leg length discrepancy in patients with unilateral high hip dislocation was 46 mm (28-65 mm); postoperatively leg length discrepancy was less than 1 cm in 11 patients, between 1 and 2 cm in 8 patients, and more than 2 cm in 2 patients. The average leg lengthening at the time of surgery was 36 mm (24-54 mm). Trendelenburg's gait changed from positive to negative in 20 hips by the last follow-up. No nerve injury occurred postoperative. CONCLUSION: Partial greater trochanter osteotomy is an effective method to render hip reduction in total hip arthroplasty for patients with high dislocation of the hip.