BMP-2/PLGA Delayed-Release Microspheres Composite Graft,Selection of Bone Particulate Diameters,and Prevention of Aseptic Inflammation for Bone Tissue Engineering

Autogenous bone grafts are widely used in the repair of bone defects. Growth factors such as bone morphogenetic protein 2 (BMP-2) can induce bone regeneration and enhance bone growth. The combination of an autogenous bone graft and BMP-2 may provide a better osteogenic effect than either treatment alone, but BMP-2 is easily inactivated in body fluid. The objective of this study was to develop a technique that can better preserve the in vivo activity of BMP-2 incorporated in bone grafts. In this study, we first prepared BMP-2/poly(lactic-co-glycolic acid) (PLGA) delayed-release microspheres, and then combined collagen, the delayed-release microspheres, and rat autologous bone particulates to form four groups of composite grafts with different combinations: collagen in group A; collagen combined with bone particulates in group B; collagen combined with BMP-2/PLGA delayed-release microspheres in group C; and collagen combined with both bone particulates and BMP-2/PLGA delayed-release microspheres in group D. The four groups of composite grafts were implanted into the gluteus maximus pockets in rats. The ectopic osteogenesis and ALP level in group D (experimental group) were compared with those in groups A, B, and C (control groups) to study whether it had higher osteogenic capability. Results showed that the composite graft design increased the utility of BMP-2 and reduced the required dose of BMP-2 and volume of autologous bone. The selection of bone particulate diameter had an impact on the osteogenetic potential of bone grafts. Collagen prevented the occurrence of aseptic inflammation and improved the osteoinductivity of BMP-2. These results showed that this composite graft design is effective and feasible for use in bone repair.     

Steroid receptor co-activator-3 promotes osteosarcoma progression through up-regulation of FoxM1

Increasing evidence suggests that the three homologous members of steroid receptor co-activator (SRC) family (SRC-1, SRC-2, and SRC-3) play key roles in enhancing cell proliferation in various human cancers, such as breast, prostate, and hepatocellular carcinoma. However, the function of SRC-3 in osteosarcoma remains largely unexplored. In the current study, we found that SRC-3, but not SRC-1 and SRC-2, was dramatically up-regulated in human osteosarcoma tissues, compared with adjacent normal tissues. To explore the functions of SRC-3 in osteosarcoma, in vitro studies were performed in MG63 and U2OS cells. SRC-3 overexpression promoted osteosarcoma cell proliferation, whereas knockdown of SRC-3 inhibits its proliferation. In support of these findings, we further demonstrated that SRC-3 up-regulated FoxM1 expression through co-activation of C/EBPγ. Together our results show that SRC-3 drives osteosarcoma progression and imply it as a therapeutic target to abrogate osteosarcoma.     

Endovascular treatment of posterior fossa arteriovenous malformations

Infratentorial arteriovenous malformations (AVM) are rare, representing only 7–15% of cerebral AVM. The concentration of eloquent neurological structures and the high rate of bleeding presentation of AVM in this location complicate the management of such lesions. New therapeutic options, especially in endovascular therapy, have fundamentally modified the treatment strategy and also the outcome of posterior fossa AVM. Between 1999 and 2013, baseline, clinical and angiographic data of cerebral AVM were prospectively collected. We analyzed data from patients treated for a posterior fossa AVM, focusing on risk factors for bleeding, and clinical and angiographic outcomes. Sixty-nine patients (mean age 34 years, male to female ratio 2:1) were consecutively treated for an infratentorial AVM. Fifty-seven presented with hemorrhage, six with focal neurologic deficits, and the remaining six patients were diagnosed incidentally. The Spetzler–Martin grade was <3 in 39 (56.5%) patients. Associated aneurysms were noted in 43.5% of patients. All patients were treated using endovascular procedures, associated with microsurgical resection in nine patients and with stereotactic radiosurgery in six. Mean follow-up was 28.5 months, with angiographic exclusion of the AVM in 72.5% of patients; 21.7% of patients presented a modified Rankin Score ⩾3 at follow-up. Endovascular embolization seems to be a secure approach for posterior fossa AVM although a large number of sessions are necessary to achieve complete obliteration. Multi-disciplinary discussion and management is crucial to obtain the best cure rate without increasing procedural risks.     

下腰椎上关节突及峡部相关解剖结构的影像学测量

目的:通过影像学方法对下腰椎的上关节突及峡部相关解剖结构进行测量,观察新型腰椎后路植骨术术中安全操作范围及其与体重及身高的相关性。方法:搜集门诊体检25～40岁正常成年人腰椎正侧位X线片(腰椎序列正常,腰椎正、侧位片显示腰椎无侧凸、畸形、旋转,腰椎骨质无异常)男、女各120例,其中,男性身高157~190cm,平均173.63cm,体重50~95kg,平均76.61kg;女性身高150~174cm,平均162.17cm,体重45~80kg,平均59.07kg。用digimizer测量软件对L3～L5椎体正位片上上关节突的长度、宽度及侧位片上上关节突的深度,峡部深度、绝对深度,植骨床长度等进行测量。利用直线回归方程分析L3～L5各椎体上关节突长度、宽度、深度和峡部深度,绝对深度,植骨床长度等是否与身高体重具有相关性。结果:男性和女性L3～L5椎体上关节突长度、宽度、深度,峡部深度,绝对深度及植骨床长度平均为1.04±0.26cm和0.98±0.25cm、0.74±0.16cm和0.72±0.19cm、2.30±0.24cm和2.17±0.24cm,0.92±0.12cm和0.84±0.11cm,1.23±0.18cm和1.16±0.18cm,2.06±0.20cm和2.01±0.17cm。男性及女性的上关节突长度、宽度、深度及峡部深度,绝对深度与身高体重无明显相关性(P>0.05)。植骨床长度与身高具有显著相关性(P<0.01),与体重无明显相关性(P>0.05)。结论:通过影像学测量可以较为准确的获得下腰椎上关节突及峡部相关解剖学数值,为新型腰椎后路植骨术劈骨操作提供了一个较为可靠地数据支持。     

Exogenous stromal cell-derived factor-1 (SDF-1) suppresses the NLRP3 inflammasome and inhibits pyroptosis in synoviocytes from osteoarthritic joints via activation of the AMPK signaling pathway

Inflammopharmacology - NLRP3 inflammasome may play a key role in OA pathogenesis. Stromal cell-derived factor-1 (SDF-1) is a homeostatic CXC chemokine. Since the role of SDF-1 in OA has not been...