BMP2 induces osteogenic differentiation through ACKR3 in mesenchymal stem cells.

In recent years, bone loss related diseases have attracted more and more attention, such as osteoporosis and osteonecrosis of the femoral head exhibited symptoms of osteopenia or insufficient bone mass in a certain stage. Mesenchymal stem cells (MSCs), which can be induced to differentiate into osteoblasts under certain conditions can provide a new solution bone disease. Herein, we deciphered the possible mechanism by which BMP2 drives the transduction of MSCs to the osteoblast lineage through ACKR3/p38/MAPK signaling. The levels of ACKR3 in femoral tissues of samples from humans with different ages and sexes were measured firstly and found that ACKR3 protein levels increase with age. In vitro cellular assays showed that ACKR3 inhibits BMP2-induced osteo-differentiation and promotes adipo-differentiation of MSCs, whereas siACKR3 exhibited the opposite effects. In vitro embryo femur culture experiment showed that inhibition of ACKR3 enhanced BMP2-induced trabecular bone formation in C57BL6/J mouse. In terms of molecular mechanisms, we found that p38/MAPK signaling might play the key role. ACKR3 agonist TC14012 suppressed the phosphorylation of p38 and STAT3 in BMP2 induced MSCs differentiation. Our findings suggested that ACKR3 might be a novel therapeutic target for the treatment of bone-associated diseases and bone-tissue engineering.

Imatinib mesylate induces mitochondria-dependent apoptosis and inhibits invasion of human pigmented villonodular synovitis fibroblast-like synovial cells.

Pigmented villonodular synovitis (PVNS) is a rare sarcoma-like disorder characterized by synovial lesions proliferation and invasion to articular cartilage for which no effective treatments are available. Imatinib mesylate (IM) is known to exert antitumor activity in some tumors, but its effects on PVNS fibroblast-like synoviocytes (PVNS-FLS) and the specific mechanism involved remain to be established. In the present study, the in vitro effects of IM on cell proliferation and survival rates were investigated in PVNS-FLS. Apoptosis induction was assessed via acridine orange/ethidium bromide (AO)/(EB) and Annexin V/PI staining as well as western blotting. The invasion ability of PVNS-FLS was evaluated by Transwell invasion chambers. IM significantly inhibited survival and invasion ability of PVNS-FLS in a dose- and time-dependent manner. The drug-treated cell groups exhibited markedly higher apoptosis, which was blocked upon pretreatment with the specific caspase-9 inhibitor Z-LEHD-FMK. Expression of cleaved caspase-9 was significantly increased and the Bcl-2 family and caspase-3 were activated following treatment with IM. Our results collectively demonstrated that IM has a strong antiproliferative effect on PVNS-FLS in vitro, attributable to induction of mitochondrial-dependent apoptosis in association with activation of caspase-9/-3 and the Bcl-2/Bax family, and exhibits significant inhibition on the invasion ability of PVNS-FLS, suggesting that IM may be useful as a novel treatment of this disease.

Nuclear ING2 expression is reduced in osteosarcoma.

Osteosarcoma is a high-grade malignant bone tumor. Loss of inhibitor of growth 2 (ING2) expression has been demonstrated in numerous types of cancers. However, no study has shown the relationship between ING2 expression and osteosarcoma. In the present study, we confirmed that the levels of ING2 mRNA and protein were lower in cancer tissues than these levels in normal tissues. Loss of nuclear ING2 protein was significantly associated with a decreased survival time of patients. Osteosarcoma cells were transfected with ING2 protein without a nuclear localization signal or intact ING2 protein to examine the effects of exogenous expression of ING2 in vitro. Compared to the control cells, intact ING2-expressing cells exhibited increased apoptosis, G1 phase arrest and senescence. Taken together, these results suggest that ING2 acts as a tumor suppressor in osteosarcoma.

The anti-tumor role and mechanism of integrated and truncated PDCD5 proteins in osteosarcoma cells.

Osteosarcoma (OS) is a high-grade malignant bone tumor. In these studies, the cell apoptosis-related gene, programmed cell death 5 gene (PDCD5), and various fragments of it, were overexpressed in the OS cell line, MG-63. The effects of PDCD5 on MG-63 cells both in vivo and in vitro were then identified. Our results indicate that PDCD5 can induce apoptosis and G(2) phase arrest in MG-63 cells. Moreover, expression of PDCD5 in established xenografted tumors was associated with a decrease in tumor size and weight. Accordingly, the survival rate of these mice was significantly higher than that of mice bearing tumors that did not express PDCD5. To analyze the signaling pathway involved, western blotting was performed. In these assays, PDCD5 was found to inhibit the Ras/Raf/MEK/ERK signaling pathway, leading to inhibition of cyclin B and CDK1. In addition, down-regulation of ERK resulted in activation of caspase 3 and caspase 9. These results are consistent with the G(2) phase arrest observed with overexpression of PDCD5. However, a G(1) phase arrest was not observed. Therefore, proteins associated with the G(1) phase of the cell cycle were overexpressed in combination with PDCD5 overexpression. Overall, these studies demonstrate the anti-tumor activity of PDCD5 in the OS cell line, MG-63, and provide insight into relevant mechanisms that may lead to novel treatments for OS.

[Closed suction drainage or non-drainage for total knee arthroplasty: a meta-analysis].

OBJECTIVES: To investigate the different effects of closed suction drainage and non-drainage for total knee arthroplasty(TKA) and to provide reference information for the choice of clinical treatment. METHODS: Randomized controlled trials (RCTs) of closed suction drainage versus non-drainage for TKA were collected from the Cochrane Library, PubMed, EMBase, Springer, CBM, CNKI, VIP and WANFANG database. Methodological quality of the RCTs was independently assessed using the Consolidated Standards of Reporting Trials (CONSORT) checklist. Data analysis was performed by RevMan Version 5.1.6 based on the methods recommended by the Cochrane Collaboration. RESULTS: Twenty-one RCTs without bias were finally enrolled, and 1920 enrolled knees were identified into drainage group (979 knees) and non-drainage group (941 knees). A lower incidence of soft tissue ecchymosis was demonstrated in the closed suction drainage group (OR = 0.30, 95%CI: 0.24 - 0.49); however, compared with the non-drainage group, more loss of blood (MD = 320.03, 95%CI: 235.31 - 404.76) and more need of homologous blood transfusion (OR = 1.83, 95%CI: 1.26 - 3.29) were found in the closed suction drainage group. In addition, there were no significant differences of postoperative infection (OR = 0.53, 95%CI: 0.22 - 1.32), deep venous thrombosis (OR = 1.00, 95%CI: 0.46 - 2.18), and the joint range of motion (MD = -0.04, 95%CI: -1.11 - 1.02) between the two groups. CONCLUSION: Based on the current evidence, no obvious advantage is demonstrated for closed suction drainage, in comparison with non-drainage for TKA.

Effects of Tongxinluo capsule on atherosclerosis obliterans in iliofemoral artery of rabbits / 中国中药杂志

<p><b>OBJECTIVE</b>To explore the effects of Tongxinluo capsule (TXL) on the atherosclerosis obliterans (ASO) in iliofemoral artery of rabbits.</p><p><b>METHOD</b>Rabbits were randomly divided into 7 groups: sham, model, TXL (0.8, 0.4, 0.2 g x kg(-1)), Tongsaimai tablet (0.8 g x kg(-1)) and Laishike (0.002 g x kg(-1)). The animal model of ASO was established with a combined method of mechanical trauma, immunologic injury and high fat fodder feeding. Rabbits were administrated the drugs 8 weeks after surgery. The levels of TC, TG, HDL-C and LDL-C in serum were determined at the time points below: pre-experiment (0 week), pre-drug administration (8 weeks post-surgery), 4 weeks after drug administration (12 weeks post-surgery), 8 weeks after drug administration (16 weeks post-surgery), 12 weeks after drug administration (20 weeks post-surgery). Meanwhile, the behavioral study was performed, the distal skin temperature of the injured hind limb detected. The histopathological changes in iliofemoral artery were examined after opacification.</p><p><b>RESULT</b>The levels of TC, TG, LDL-C, VLDL-C and TC/HDL-C were decreased significantly in serum of ASO rabbits. The severity of lameness in the injured hind limb was improved. The distal skin temperature was increased. The thickness and the ratio of intima area of the iliofemoral artery of the injured hind limb were decreased, while the stenosis extent was improved.</p><p><b>CONCLUSION</b>TXL might be beneficial to modulate blood lipid, as well as the prevention and treatment for ASO.</p>

Effects of Refined Xuefu Capsule on vascular patency rate after femoral-popliteal bypass / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To observe the effects of refined Xuefu Capsule (RXC) in patients with arteriosclerosis obliterans (ASO) after femoral-popliteal bypass (FPB).</p><p><b>METHODS</b>Thirty-eight ASO patients with 41 limbs underwent FPB were randomly assigned to two groups: the control group (18 cases with 20 operated limbs) and the RXC group (20 cases with 21 operated limbs). All patients received long-term anticoagulant treatment with Warfarin, and RXC was given to the RXC group additionally for 3 months. Changes of clinical symptoms, blood coagulating function, as well as the condition of vascular patency and ankle arm index (AAI) were assessed 6 and 12 months after operation.</p><p><b>RESULTS</b>Clinical symptoms were improved in all the patients after operation. One year after operation, incidence of intermittent claudication and amputation rate in the RXC group was 20% and 5 %, being lower than the respective rate (56% and 17%) in the control group (P < 0.05); the patency rate was 86% in the RXC group, being higher than that in the control group (65%, P<0.05). Six and 12 months after operation, AAI was 0.73 +/- 0.24 and 0.69 +/- 0.19 respectively in the RXC group, being significantly higher than that in the control group (0.45 +/- 0.17 and 0.41 +/- 0.23, P < 0.05) at the corresponding time points.</p><p><b>CONCLUSION</b>RXC could obviously increase the patency rate 12 months after FPB, improve the clinical symptoms and alleviate the symptom of limb ischemia in ASO patients.</p>