TPX2 upregulates MMP13 to promote the progression of lipopolysaccharide-induced osteoarthritis.

Purpose: This study seeks to identify potential clinical biomarkers for osteoarthritis (OA) using bioinformatics and investigate OA mechanisms through cellular assays. Methods: Differentially Expressed Genes (DEGs) from GSE52042 (four OA samples, four control samples) were screened and analyzed with protein-protein interaction (PPI) analysis. Overlapping genes in GSE52042 and GSE206848 (seven OA samples, and seven control samples) were identified and evaluated using Gene Set Enrichment Analysis (GSEA) and clinical diagnostic value analysis to determine the hub gene. Finally, whether and how the hub gene impacts LPS-induced OA progression was explored by in vitro experiments, including Western blotting (WB), co-immunoprecipitation (Co-IP), flow cytometry, etc. Result: Bioinformatics analysis of DEGs (142 up-regulated and 171 down-regulated) in GSE52042 identified two overlapping genes (U2AF2, TPX2) that exhibit significant clinical diagnostic value. These genes are up-regulated in OA samples from both GSE52042 and GSE206848 datasets. Notably, TPX2, which AUC = 0.873 was identified as the hub gene. In vitro experiments have demonstrated that silencing TPX2 can alleviate damage to chondrocytes induced by lipopolysaccharide (LPS). Furthermore, there is a protein interaction between TPX2 and MMP13 in OA. Excessive MMP13 can attenuate the effects of TPX2 knockdown on LPS-induced changes in OA protein expression, cell growth, and apoptosis. Conclusion: In conclusion, our findings shed light on the molecular mechanisms of OA and suggested TPX2 as a potential therapeutic target. TPX2 could promote the progression of LPS-induced OA by up-regulating the expression of MMP13, which provides some implications for clinical research.

Methyl 3,4-dihydroxybenzoate inhibits RANKL-induced osteoclastogenesis via Nrf2 signaling in vitro and suppresses LPS-induced osteolysis and ovariectomy-induced osteoporosis in vivo.

Osteoporosis deteriorates bone mass and biomechanical strength and is life-threatening to the elderly. In this study, we show that methyl 3,4-dihydroxybenzoate (MDHB), an antioxidant small-molecule compound extracted from natural plants, inhibits receptor activator of nuclear factor-κB (NF-κB) ligand (RANKL)-induced osteoclastogenesis in vitro. Furthermore, MDHB attenuates the activation of mitogen-activated protein kinase (MAPK) and NF-κB pathways by reducing the levels of reactive oxygen species (ROS), which leads to downregulated protein expression of c-Fos and nuclear factor of activated T cells c1 (NFATc1). We also confirm that MDHB upregulates the protein expression of nuclear factor-erythroid 2-related factor 2 (Nrf2), an important transcription factor involved in ROS regulation, by inhibiting the ubiquitination-mediated proteasomal degradation of Nrf2. Next, animal experiments show that MDHB has an effective therapeutic effect on lipopolysaccharide (LPS)- and ovariectomized (OVX)-induced bone loss in mice. Our study demonstrates that MDHB can upregulate Nrf2 and suppress excessive osteoclast activity in mice to treat osteoporosis.

RCAN1.4 suppresses the osteosarcoma growth and metastasis via interfering with the calcineurin/NFAT signaling pathway.

Calcipressin-1, also known as a regulator of calcineurin 1 (RCAN1), is one of the families of endogenous regulators of calcineurin activation and can specifically constrain the activity of calcineurin, but its function in osteosarcoma is still unknown. Firstly, we examined the protein level of RCAN1 in osteosarcoma specimens was lower than that of chondroma specimens. RCAN1.4 rather than RCAN1.1 had a higher endogenous protein level in six osteosarcoma cell lines by western blot. Further, we created stable RCAN1.4-deficient 143B and Hos cells using CRISPR-Cas9. RCAN1.4 loss promoted tumor growth in subcutaneous xenograft models. RCAN1.4 knockdown promoted tumor metastases to the lungs using intravenous metastasis models. Furthermore, we found that higher activity of calcineurin in RCAN1.4-deficient cells enhanced the nuclear translocation of NFATc1 to induce the cyclin D1 and MMPs expression. In addition, RCAN1.4 overexpression restrained osteosarcoma cell growth and invasion and inhibited the activity of calcineurin. Finally, we discovered that conditioned medium (20%) derived from RCAN1.4-deficient cells significantly promoted osteoclastogenesis, indicating Receptor Activator of Nuclear factor κB (RANK) signaling activation during osteosarcoma metastasis. In conclusion, RCAN1.4 may be a potential therapeutic target for osteosarcoma.

Hypoxia-Mimicking Cobalt-Doped Borosilicate Bioactive Glass Scaffolds with Enhanced Angiogenic and Osteogenic Capacity for Bone Regeneration.

The osteogenic capacity of synthetic bone substitutes is will be highly stimulated by a well-established functional vascularized network. Cobalt (Co) ions are known that can generate a hypoxia-like response and stimulates the production of kinds of angiogenic factors. Herein, we investigated the mechanism of cobalt-doped bioactive borosilicate (36B2O3, 22CaO, 18SiO2, 8MgO, 8K2O, 6Na2O, 2P2O5; mol%) glass scaffolds for bone tissues repairing and blood vessel formation in the critical-sized cranial defect site of rats and their effects on the hBMSCs in vitro were researched. The scaffolds can control release Co2+ ions and convert into hydroxyapatite soaking in simulative body fluids (SBF). The fabircated scaffolds without cytotoxic strongly improves HIF-1α generation, VEGF protein secretion, ALP activity and upregulates the expression of osteoblast and angiogenic relative genes in hBMSCs. Eight weeks after implantation, the bioactive glass scaffolds with 3wt % CoO remarkablely enhance bone regeneration and blood vascularized network at the defective site. In conclusion, as a graft material for bone defects, low-oxygen simulated cobalt-doped bioactive glass scaffold is promising.

[Analysis on risk factors of functional recovery after intramedullary nail fixation for femoral intertrochanteric fractures in elderly patients].

OBJECTIVE: To investigate the risk factors of functional recovery after intramedullary nail fixation for femoral intertrochanteric fracture in elderly patients, and to propose corresponding measures to promote postoperative hip function recovery. METHODS: From June 2012 to June 2015, 74 patients after intramedullary nail fixation surgery were analyzed, including 33 males and 41 females, with an average age of(75.07±7.89) years old, and divided into well-function group(55 patients) and bad-function group(19 patients) according to Sanders function criterion. Age, gender, bone density, fracture type, systemic disease, complication, rehabilitation exercises with therapist or not, nourishment state, anesthesia method, fracture reduction condition, ASA classification, tip apex distance were reviewed and analyzed by t test, non-parametric test, χ² test and Logistic analysis. RESULTS: Univariate analysis showed that age, bone density, nourishment state, ASA classification, anesthesia method, fracture reduction condition, rehabilitation exercises with therapist, and tip apex distance were the risk factors for the recovery of hip function. Logistic analysis showed that bone density(P=0.006, OR=0.077), rehabilitation exercises with therapist(P=0.006, OR=0.070), ASA classification(P<0.001, OR=0.049), nourishment state (P=0.046, OR=0.188) were the risk factors for the functional recovery. CONCLUSIONS: Bone density, rehabilitation exercises with therapist, ASA classification, nourishment state were the risk factors for the functional recovery of intramedullary nail fixation for intertrochanteric fracture in elderly patients. Multidisciplinary cooperation and fast track surgery system should be set up to promoting the hip functional recovery.

[Complications of percutaneous kyphoplasty non-related with bone leakage in treating osteoporotic thoracolumbar vertebral compression fractures].

OBJECTIVE: To analyze the complications of percutaneous kyphoplasty except bone leakge for the treatment of osteoporotic thoracolumbar vertebral compression fractures. METHODS: From October 2008 to October 2012,178 patients with 224 osteoporotic vertebral compression fractures were treated with percutaneous kyphoplasty under local anethsia. There were 72 males and 106 females,ranging in age from 58 to 92 years old,with an average of 75.3 years,including 93 thoracic vertebrae and 131 lumbar vertebrae. The complications except bone cement leakage were analyzed during operation and after operation. RESULTS: All operations were successful and all patients were followed up from 12 to 60 months with an average of 26.2 months. No death was found. Bone cement leakage occurred in 27 cases, about 15.1% in 178 cases; and complications except bone cement leakage occurred in 15 cases. There was 1 case with cardiac arrest,was completely recovery by cardiopulmonary resuscitation (CPR) immediately; and 1 case with temporary absence of breathing,was recovery after treatment. There were 3 cases with fall of blood pressure and slower of heart rate; 1 case with intestinal obstruction; 2 cases with local hematoma and 1 case with intercostal neuralgia. Vertebral body fractures of 2 cases were split by bone cement and the fractures of adjacent body occurred in 4 cases. CONCLUSION: It's uncommon complication except bone cement leakge in treatment of osteoporotic thoracolumbar vertebral compression fractures with percutaneous kyphoplasty. The complication of cardiopulmonary system is a high risk in surgery; and cytotoxicity of bone cement,nervous reflex,fat embolism and alteration of intravertebral pressure may be main reasons.

[Analysis of perioperative complications of percutaneous kyphoplasty for osteoporotic vertebral compression fracture].

OBJECTIVE: To analyze the perioperative complications of percutaneous kyphoplasty (PKP) for osteoporotic vertebral compression fracture. METHODS: From June 2009 to December 2011, 63 patients with osteoporotic vertebral compression fracture underwent PKP, there were 18 males and 45 females with an average age of 75.3 years ( ranged, 62 to 91). All patients with severe back pain and without neurological symptoms and signs, which were confirmed by X-ray and MRI. Among them,there were 63 cases with severe osteoporosis, 37 cases with hypertension, 10 with coronary artery disease, 29 with anemia, 26 with diabetes, 11 with chronic obstructive pulmonary diseases and 8 with gastritis and peptic ulcer. The common perioperative complications were retropectively reviewed. RESULTS: Preoperative complications occured in 9 cases (14.3%), including hypostatic pneumonia (1 case), electrolyte disturbances (2 cases), urinary tract infection (2 cases), moderate anemia(2 cases),electrolyte disturbances combined with moderate anemia (1 case), hypostatic pneumonia combined with delirium (1 case). Intraoperative and postoperative. complications occurred in 17 cases (26.9%), there were bone cement correlated complications in 9 cases (14.3%), in which 2 cases of toxic reaction of bone cement and 7 cases of leakage (2 cases had clinical symptoms); there were non-bone cement correlated complications in 3 cases (4.8%), in which 1 case of focal hematoma caused by paracentesis, 1 case of transient nerve injury, 1 case of left intercostal neuralgia;there were transient hyperpathia in 5 cases after operation. All complications result in no severe consequence after treatment. CONCLUSION: Perioperative complications of percutaneous kyphoplasty are not uncommon,however,these complications may not cause serious consequence after active treatment,so prevention and treatment are important for it.

[Treatment of senile osteoporotic vertebral compression fractures with percutaneous kyphoplasty under local anesthesia].

OBJECTIVE: To evaluate the clinical outcomes of percutaneous kyphoplasty (PKP) in treating senile osteoporotic vertebral compression fractures under local anesthesia. METHODS: From May 2007 to May 2010,129 patients with osteoporotic vertebral compression fractures were treated with PKP under local anesthesia. There were 47 males and 82 females, ranging in age from 61 to 92 years old,with an average of 73.7 years old,including 88 segments of thoracic vertebrae and 101 segments of lumbar vertebrae. Visual analogue scale (VAS),height of vertebral body,Cobb's angle were evaluated before and after operation. RESULTS: Operations were performed successfully in all patients and these patients were followed up from 24 to 60 months with an average of 34.2 months. Preoperative,postoperative two weeks and at final follow-up,VAS score was 7.9+/-2.5,2.8+/-1.8,3.0+/-2.2,respectively;Cobb angle was (28.3+/-13.7)degree, (16.2+/-9.8)degree, (19.1+/-10.3)degree, respectively. There was significant difference between postoperative and preoperative, and between at final follow up and preoperative (P<0.05). The height of vertebral body obtained partial recovery. Bone cement leakage occurred in 23 vertebrae (with proportion of 17.8%) during operation,among one patient with temporary clinical symptom of radiculalgia. All lumbago obtained obviously anesis after operation, 1 case complicated with respiratory depression and recovered after resuscitation; 1 case complicated with intestinal obstruction and improved after treatment, 1 case complicated with fracture separation of vertebral body by bone cement, and 4 cases complicated with fracture of adjacent vertebral body. CONCLUSION: Percutaneous vertebral kyphoplasty is an effective method for treatment of senile osteoporotic vertebral compression fractures,which can expeditiously relieve pain and effectively recovery height of vertebral body and Cobb angle,it has advantages of minimal invasive. The results of short and mid-term follow-up were satisfactory, long-term follow-up is still needed. Correctly choosing the operative indication and improving surgical technique may avoid complications, especially bone cement leakage which is the most frequent complication.

[Bernese periacetabular osteotomy for the treatment of severe hip dysplasia].

OBJECTIVE: To analyze the mid-term clinical and radiographic results obtained with the Bernese periacetabular osteotomy for the treatment of severe hip dysplasia. METHODS: From October 1997 to December 2002 20 hips of 18 patients were classified as having severe acetabular dysplasia (Severin classification Grade IVb). Preoperatively, all patients had hip pain, and sufficient hip joint congruency on functional radiographs. All 20 hips underwent Bernese periacetabular osteotomy. Postoperatively, the hips were assessed radiographically on center edge angle (CE), acetabular roof obliquity and the progression of osteoarthritis. Clinical results and hip function were measured with the Harris hip score at an average of 6.2 years follow-up. RESULTS: Comparison of preoperative and follow-up radiographs demonstrated significant improvements in the lateral CE angle, the anterior CE angle, and roof obliquity. The average Harris hip score improved from 78.5 points preoperatively to 91.1 points at the time of the latest follow-up. Fourteen of 18 patients were satisfied with the result of the surgery, and 16 of 20 hips had a good or excellent clinical result. Under-correction occurred in 5 hips. CONCLUSIONS: The Bernese periacetabular osteotomy is an effective procedure for surgical correction of the severe dysplastic hip. This osteotomy can predictably obtain major reorientation of the acetabulum in all planes. The clinical results in the mid-term follow-up are encouraging.

Acetabular medial wall displacement osteotomy in total hip arthroplasty: a technique to optimize the acetabular reconstruction in acetabular dysplasia.

Twenty-six patients (30 hips) who had acetabular dysplasia were operated on by circumferential acetabular medial wall displacement osteotomy to reconstruct the acetabulum during total hip arthroplasty. All patients had cementless acetabular components implanted. The average acetabular component size was 50 mm (range, 44-56 mm). Only 2 hips needed structural bone graft. The mean follow-up period was 22 months (range, 6-32 months). Harris hip score had changed from 47.31 (range, 19-69 points) to 94.69 (range, 85-100 points) postoperatively (P < .01). Using the Ranawat acetabular triangle to determine the optimal hip center of rotation, the postoperative hip biomechanical environment had been improved. Our short-term follow-up suggests this technique is reliable and reproducible and generally avoids the use of bone graft and graft site morbidity. In addition, it allows the use of standard modular cementless components in patients with acetabular dysplasia.