冰茶栓对骨癌痛大鼠骨溶解的影响

目的观察冰茶栓对W256细胞诱导的骨癌痛大鼠骨溶解的影响。方法将40只雌性SD大鼠分为假手术组、模型组、邦罗力组及冰茶栓组,采用骨髓腔注射W256癌细胞复制骨癌痛模型;模型复制第13天开始,假手术组和模型组给予空白栓,邦罗力组给予邦罗力20μg/kg,冰茶栓组给予冰茶栓101mg/kg。末次给药后,对各组大鼠患肢进行X线摄片并评分以观察骨溶解情况,采用苏木精-伊红染色观察骨组织病理学变化,采用抗酒石酸酸性磷酸酶染色观察破骨细胞数量。结果冰茶栓可明显降低骨癌痛大鼠患肢X线评分(P0.01),改善肿瘤引起的骨损伤,降低骨组织破骨细胞数量(P0.01)。结论冰茶栓对W256细胞诱导的骨癌痛大鼠骨溶解具有较好的抑制作用。     

力学刺激在破骨细胞分化中的作用

骨组织细胞主要有成骨细胞、破骨细胞、骨细胞3种类型,与细胞外基质共同维持骨的结构完整性和功能性。破骨细胞专门负责骨吸收,通过释放酸性物质和蛋白水解酶降解骨基质,发挥骨吸收作用;通过与成骨细胞相互协调,共同维持骨稳态。破骨细胞增多,导致骨吸收增加,从而引起骨质疏松症等骨骼疾病;破骨细胞生成过少,将导致骨吸收减弱等相关疾病,例如骨硬化症。因此,对于破骨细胞功能的精确调控,在维持骨稳态的平衡中发挥极为关键的作用。既往研究多从生物化学角度解释和阐述各种生物因素对破骨细胞的调控。然而越来越多的研究证实,力学刺激在破骨细胞分化过程中发挥着重要的作用。本文着眼于力学刺激对破骨细胞分化的影响,讨论力学刺激在其中可能发挥的作用,并对该领域的新发现以及未来的发展进行探讨。     

MicroRNA-21与骨质疏松症相关性的研究进展

骨质疏松症(osteoporosis,OP)是一种以易骨折为特点的全身代谢性骨骼疾病。在老龄化程度不断加剧的当今社会,其发病率逐年呈现显著上升趋势,尤其是骨质疏松性骨折导致的后遗症、副损伤给社会及患者带来极大的经济和生活负担。近年来诸多研究发现microRNA具有明确的抗骨质疏松作用,随着基因疗法应用的推广,microRNA在临床治疗骨质疏松起到了很好的靶向作用,同时相关文献阐释,尤其是其家族成员microRNA-21可通过调控成骨细胞和破骨细胞的分化与功能,在OP等骨疾病的发生发展过程中起着重要作用。本文将通过对microRNA-21在骨质疏松中的相关作用机制进行综述,旨在为OP靶向治疗及相关分子机制研究提供理论依据和新的思路。     

融合骨缝重新打开为上颌骨扩弓提供了治疗新思路

背景:上颌骨横向发育不足是临床上常见的错(牙合)畸形,种植体支抗辅助上颌快速扩弓等新兴上颌骨扩弓方法为成人上颌骨扩弓提供了新的可能.目的:综述上颌骨扩弓机制的研究进展,从而更好地寻找骨缝间骨再生的方法,获得满足临床需要的扩弓量以及扩弓效果的稳定性.方法:检索万方、中国期刊全文数据库(CNKI)、Pubmed、Web o...     

B淋巴细胞及相关细胞因子在骨免疫系统中对破骨细胞分化的作用

背景:作为免疫系统组成中重要的免疫细胞——B淋巴细胞可参与骨代谢过程的调控,对破骨细胞的分化发育发挥着重要的作用.目的:就B淋巴细胞的特征及其对破骨细胞分化过程产生的作用进行综述.方法:以关键词骨免疫;B细胞;破骨细胞在CNKI、万方等数据库中检索;以关键词osteoimmunology;B lymphocyte...     

抗骨质疏松药物应用的依据：骨生化代谢标志物及骨组织病理学

背景：目前国际上公认双能 X 射线吸收测定法为诊断骨质疏松症的金标准,但常由于测量部位异位骨化、骨质增生等因素使得测量结果存在误差。目的：探讨骨代谢标志物在老年骨质疏松骨折诊疗中的临床意义以及它与骨密度和骨组织形态病理学改变的相关性。方法：选取50例需行手术治疗的老年骨质疏松骨折患者,行骨生化4项检测,其中抗酒石酸酸性磷酸酶5b(TRACP 5b)检测值明显增高患者25例(标记为抗酒石酸酸性磷酸酶5b 升高组),骨碱性磷酸酶(BAP)检测值明显升高患者25例(标记为骨碱性磷酸酶升高组)。术中抽取两组各8例患者骨折断端部分骨组织,苏木精-伊红染色普通光镜检查和扫描电镜检查病理学改变。术后,抗酒石酸酸性磷酸酶5b 升高组患者使用鲑鱼降钙素抗骨质疏松治疗,骨碱性磷酸酶升高组患者使用骨肽注射液抗骨质疏松治疗,6个月后再次检测骨密度和骨生化4项。结果与结论：两组患者术前骨密度和骨生化4项检查结果相比较差异无显著性意义(P >0.05)。抗酒石酸酸性磷酸酶5b 升高组患者骨折断端骨组织病理检查示成骨细胞减少、破骨细胞增多;骨碱性磷酸酶升高组患者骨折断端骨组织病理检查示成骨细胞减少;两组骨小梁/骨面积比值均降低,且抗酒石酸酸性磷酸酶5b 升高组较骨碱性磷酸酶升高组降低程度差异有显著性意义(P <0.05)。扫描电镜检查示两组破骨细胞都较正常组活跃,抗酒石酸酸性磷酸酶5b 升高组骨小梁较骨碱性磷酸酶升高组稀松明显,吸收空泡增大。两组于术后使用抗骨质疏松药物治疗,两组治疗前与治疗后骨密度和骨生化4项检测结果差异有显著性意义(P <0.05)。结果显示：①骨代谢标志物检测能明确患者骨组织是以成骨细胞功能和数量减低还是以破骨细胞功能和数量增加为主,以便指导临床针对性使用抗骨质疏松药物。②骨折断端骨组织形态病理学检查能更好地反映患者骨组织内成骨细胞、破骨细胞和骨小梁等状况。骨质疏松患者针对性使用抗骨质疏松药物治疗能提高疗效、降低相关并发症。     

Enhancement of osteoclastic bone resorption and suppression of osteoblastic bone formation in response to reduced mechanical stress do not occur in the absence of osteopontin

Reduced mechanical stress to bone in bedridden patients and astronauts leads to bone loss and increase in fracture risk which is one of the major medical and health issues in modern aging society and space medicine. However, no molecule involved in the mechanisms underlying this phenomenon has been identified to date. Osteopontin (OPN) is one of the major noncollagenous proteins in bone matrix, but its function in mediating physical-force effects on bone in vivo has not been known. To investigate the possible requirement for OPN in the transduction of mechanical signaling in bone metabolism in vivo, we examined the effect of unloading on the bones of OPN(-/-) mice using a tail suspension model. In contrast to the tail suspension-induced bone loss in wild-type mice, OPN(-/-) mice did not lose bone. Elevation of urinary deoxypyridinoline levels due to unloading was observed in wild-type but not in OPN(-/-) mice. Analysis of the mechanisms of OPN deficiency-dependent reduction in bone on the cellular basis resulted in two unexpected findings. First, osteoclasts, which were increased by unloading in wild-type mice, were not increased by tail suspension in OPN(-/-) mice. Second, measures of osteoblastic bone formation, which were decreased in wild-type mice by unloading, were not altered in OPN(-/-) mice. These observations indicate that the presence of OPN is a prerequisite for the activation of osteoclastic bone resorption and for the reduction in osteoblastic bone formation in unloaded mice. Thus, OPN is a molecule required for the bone loss induced by mechanical stress that regulates the functions of osteoblasts and osteoclasts.     

The role of osteoclasts in bone tissue engineering

The success of scaffold‐based bone regeneration approaches strongly depends on the performance of the biomaterial utilized. Within the efforts of regenerative medicine towards a restitutio ad integrum (i.e. complete reconstruction of a diseased tissue), scaffolds should be completely degraded within an adequate period of time. The degradation of synthetic bone substitute materials involves both chemical dissolution (physicochemical degradation) and resorption (cellular degradation by osteoclasts). Responsible for bone resorption are osteoclasts, cells of haematopoietic origin. Osteoclasts play also a crucial role in bone remodelling, which is essential for the regeneration of bone defects. There is, however, surprisingly limited knowledge about the detailed effects of osteoclasts on biomaterials degradation behaviour. This review covers the relevant fundamental knowledge and progress made in the field of osteoclast activity related to biomaterials used for bone regeneration. In vitro studies with osteoclastic precursor cells on synthetic bone substitute materials show that there are specific parameters that inhibit or enhance resorption. Moreover, analyses of the bone–material interface reveal that biomaterials composition has a significant influence on their degradation in contact with osteoclasts. Crystallinity, grain size, surface bioactivity and density of the surface seem to have a less significant effect on osteoclastic activity. In addition, the topography of the scaffold surface can be tailored to affect the development and spreading of osteoclast cells. The present review also highlights possible areas on which future research is needed and which are relevant to enhance our understanding of the complex role of osteoclasts in bone tissue engineering. Copyright © 2014 John Wiley & Sons, Ltd.     

IRAK4 inhibition: a promising strategy for treating RA joint inflammation and bone erosion

Flares of joint inflammation and resistance to currently available biologic therapeutics in rheumatoid arthritis (RA) patients could reflect activation of innate immune mechanisms. Herein, we show that a TLR7 GU-rich endogenous ligand, miR-Let7b, potentiates synovitis by amplifying RA monocyte and fibroblast (FLS) trafficking. miR-Let7b ligation to TLR7 in macrophages (MΦs) and FLSs expanded the synovial inflammatory response. Moreover, secretion of M1 monokines triggered by miR-Let7b enhanced Th1/Th17 cell differentiation. We showed that IRAK4 inhibitor (i) therapy attenuated RA disease activity by blocking TLR7-induced M1 MΦ or FLS activation, as well as monokine-modulated Th1/Th17 cell polarization. IRAK4i therapy also disrupted RA osteoclastogenesis, which was amplified by miR-Let7b ligation to joint myeloid TLR7. Hence, the effectiveness of IRAK4i was compared with that of a TNF inhibitor (i) or anti-IL-6R treatment in collagen-induced arthritis (CIA) and miR-Let7b-mediated arthritis. We found that TNF or IL-6R blocking therapies mitigated CIA by reducing the infiltration of joint F480⁺iNOS⁺ MΦs, the expression of certain monokines, and Th1 cell differentiation. Unexpectedly, these biologic therapies were unable to alleviate miR-Let7b-induced arthritis. The superior efficacy of IRAK4i over anti-TNF or anti-IL-6R therapy in miR-Let7b-induced arthritis or CIA was due to the ability of IRAK4i therapy to restrain the migration of joint F480⁺iNOS⁺ MΦs, vimentin⁺ fibroblasts, and CD3⁺ T cells, in addition to negating the expression of a wide range of monokines, including IL-12, MIP2, and IRF5 and Th1/Th17 lymphokines. In conclusion, IRAK4i therapy may provide a promising strategy for RA therapy by disconnecting critical links between inflammatory joint cells.     

Identifying early osteoclastic resorptive lesions in feline teeth: a model for understanding the origin of multiple idiopathic root resorption

Background and Objective:  Domestic cats commonly suffer from external osteoclastic tooth resorption, a disease with many similarities to human multiple idiopathic root resorption. In both diseases, it is unclear whether anatomical features of the tooth surface are associated with a predisposition for resorptive lesions. The aim of the present study was to investigate the origin and progression of early feline osteoclastic resorptive lesions in teeth exhibiting no clinical signs of disease.
Material and Methods:  The entire surfaces of 138 teeth from 13 adult cats were analysed using back-scattered electron microscopy. The distribution of lesions was assessed by tooth type, location and between individuals.
Results:  Seventy-three (53%) teeth showed at least one resorptive lesion. Eleven (85%) cats had lesions, and there was a significant association between increasing age and incidence of resorptive lesions. The highest frequency occurred in mandibular molars (82%). On average, there were 3.5 lesions per tooth. Fifty-two (38%) teeth featured resorptive lesions at the cemento–enamel junction. Twenty-three per cent of teeth with resorptive lesions showed evidence of repair of lesions that was limited to the root surface. There was no evidence of repair of resorptive lesions at the cemento–enamel junction.
Conclusion:  Resorption is prevalent without evidence of clinical disease, and occured at younger ages than previously reported. It can initiate anywhere on the root surface, but lack of repair of lesions at the cemento–enamel junction indicates that mechanisms of replacement are absent or compromised in this region. Whereas resorption of the root may undergo repair, resorption at the cervix may progress to clinically evident lesions.