Current and future uses of skeletal stem cells for bone regeneration

The postnatal skeleton undergoes growth, modeling, and remodeling. The human skeleton is a composite of diverse tissue types, including bone, cartilage, fat, fibroblasts, nerves, blood vessels, and hematopoietic cells. Fracture nonunion and bone defects are among the most challenging clinical problems in orthopedic trauma. The incidence of nonunion or bone defects following fractures is increasing. Stem and progenitor cells mediate homeostasis and regeneration in postnatal tissue, including bone tissue. As multipotent stem cells, skeletal stem cells (SSCs) have a strong effect on the growth, differentiation, and repair of bone regeneration. In recent years, a number of important studies have characterized the hierarchy, differential potential, and bone formation of SSCs. Here, we describe studies on and applications of SSCs and/or mesenchymal stem cells for bone regeneration.     

Approaches to promoting bone marrow mesenchymal stem cell osteogenesis on orthopedic implant surface

Bone marrow-derived mesenchymal stem cells(BMSCs) play a critical role in the osseointegration of bone and orthopedic implant. However, osseointegration between the Ti-based implants and the surrounding bone tissue must be improved due to titanium's inherent defects. Surface modification stands out as a versatile technique to create instructive biomaterials that can actively direct stem cell fate. Here, we summarize the current approaches to promoting BMSC osteogenesis on the surface of titanium and its alloys. We will highlight the utilization of the unique properties of titanium and its alloys in promoting tissue regeneration, and discuss recent advances in understanding their role in regenerative medicine. We aim to provide a systematic and comprehensive review of approaches to promoting BMSC osteogenesis on the orthopedic implant surface.     

Hommes modernes en Asie septentrionale

The huge asiatic area does not show clear cut traditions but only fundamental tendencies proper to the human mind considered in its whole evolution mechanism. These tendencies are both clear and powerful: lightness of the skulls, technical blanks lighter, bone tools, pendants, and high mobility. The cultural European categories cannot be applied as such since the anthropological units were fuzzy, just like the huge steppes where they have developed. Europe just represents marginal caricatures and fixed of these general movements acting like waves perpetual and powerful.     

艾拉莫德对难治性类风湿关节炎患者骨密度和血清B-ALP、CTX-I的机制分析

摘要 目的：探讨艾拉莫德对难治性类风湿关节炎患者骨密度和血清骨碱性磷酸酶（B-ALP）、I型胶原交联羧基末端肽（CTX-I）的机制。方法：选择2019年1月至2020年12月我院接诊的134例难治性类风湿关节炎患者,通过随机数表法分为观察组和对照组,每组67例。对照组给予甲氨蝶呤联合依那西普治疗,观察组给予艾拉莫德片联合依那西普治疗,均连续治疗12周。比较两组临床缓解率、实验室指标、类风湿关节炎患者病情评价（DAS28评分）、骨密度、血清B-ALP、CTX-I的变化和不良反应。结果：治疗后,观察组临床缓解率为90.00%,明显高于对照组72.50%（P＜0.05）;观察组红细胞沉降率（ESR）、C反应蛋白（CRP）、类风湿因子（RF）、抗环挂氨酸肽抗体（抗-CCP）表达和DAS28评分分别为（23.53±2.77）mm/h、（11.73±2.30）mg/L、（17.45±3.08）U/L、（43.22±7.17）RU/mL、（2.74±0.34）分,均明显低于对照组的（31.27±5.04）mm/h、（19.11±2.12）mg/L、（24.47±2.59）U/L、（55.23±7.44）RU/mL、（3.21±0.50）分,差异有统计学意义（P＜0.05）;观察组骨密度、血清B-ALP分别为（0.83±0.05）g/cm3、（117.02±15.65）U/L,均明显高于对照组（0.77±0.04）g/cm3、（101.19±9.59）U/L,观察组CTX-I为（0.36±0.04）μg/L,明显低于对照组（0.47±0.04）μg/L,差异有统计学意义（P＜0.05）;两组不良反应总发生率分别为4.44%和2.22%,差异无统计学意义（P＞0.05）。结论：艾拉莫德联合依那西普治疗难治性类风湿关节炎效果显著,可明显改善骨密度、血清B-ALP、CTX-I的表达,提高临床缓解率,安全性好,值得应用推广。     

六味地黄丸联合小剂量雌孕激素替代疗法对围绝经期综合征患者性激素、骨密度和血脂的影响

摘要 目的：探讨六味地黄丸联合小剂量雌孕激素替代疗法对围绝经期综合征（PMS）患者性激素、骨密度和血脂的影响。方法：研究对象选取2018年12月~2020年5月期间我院接收的PMS患者93例,根据乱数表法将患者随机分为对照组（n=46）和研究组（n=47）,对照组给予小剂量雌孕激素替代疗法,研究组给予六味地黄丸联合小剂量雌孕激素替代疗法,28d为一个治疗周期,对比两组患者治疗3个周期后的疗效、性激素、腰椎L2～L4骨密度、血脂、子宫内膜厚度及不良反应。结果：治疗3个周期后,研究组的总有效率为91.49%（43/47）,高于对照组的76.09%（35/46）（P<0.05）。治疗3个周期后,研究组改良Kupperman评分表（KMI）、总胆固醇（TC）、甘油三酯（TG）、低密度脂蛋白胆固醇（LDL-C）、促卵泡刺激素(FSH)、促黄体生成素(LH)低于对照组,高密度脂蛋白胆固醇（HDL-C）、子宫内膜厚度、腰椎L2～L4骨密度、雌二醇（E2）高于对照组（P<0.05）。两组不良反应总发生率对比差异无统计学意义（P>0.05）。结论：六味地黄丸联合小剂量雌孕激素替代疗法治疗PMS患者,可有效缓解临床症状,提高骨密度,改善PMS患者的性激素及血脂水平,疗效确切。     

网袋强化椎体成形术在骨质疏松椎体骨折治疗中的经验教训

摘要 目的：探讨和总结使用网袋强化椎体成形术在骨质疏松椎体骨折围手术期的注意事项及相关对策。方法：回顾性分析2017年6月到2020年6月3年时间内,使用网袋强化椎体成形术治疗骨质疏松性椎体骨折患者共计112例。统计和比较患者在围手术期的各项指标,分析穿刺失败的原因及相关危险因素。结果：112例患者共涉及138个椎体。其中一期穿刺失败率（骨水泥分布不佳）为47个,占34.0%。骨水泥注入3 mL以下者为19个,占13.8%。骨水泥渗漏为36个,占26.1%。所有患者在术后3天及3月复查, VAS评分和ODI评分较前均有显著改善(P<0.05)。所有患者均未出现严重并发症(P>0.05)。结论：网袋强化椎体成形术在骨质疏松性椎体骨折的治疗中是一种理想的治疗方式,但在具体过程中仍有相关的经验和教训需要整理和总结。     

Bone phenotype of P2X4 receptor knockout mice: implication of a P2X7 receptor mutation?

Transgenic and knockout animal models are widely used to investigate the role of receptors, signaling pathways, and other peptides and proteins. Varying results are often published on the same model from different groups, and much effort has been put into understanding the underlying causes of these sometimes conflicting results. Recently, it has been shown that a P2X4R knockout model carries a so-called passenger mutation in the P2X7R gene, potentially affecting the interpretation of results from studies using this animal model. We therefore report this case to raise awareness about the potential pitfalls using genetically modified animal models, especially within P2 receptor research. Although purinergic signaling has been recognized as an important contributor to the regulation of bone remodeling, the process that maintains the bone quality during life, little is known about the role of the P2X4 receptor (P2X4R) in regulation of bone remodeling in health and disease. To address this, we analyzed the bone phenotype of P2rx4tm1Rass (C57BL/6J) knockout mice and corresponding wildtype using microCT and biomechanical testing. Overall, we found that the P2X4R knockout mice displayed improved bone microstructure and stronger bones in an age- and gender-dependent manner. While cortical BMD, trabecular BMD, and bone volume were higher in the 6-month-old females and 3-month-old males, this was not the case for the 3-month-old females and the 6-month-old males. Bone strength was only affected in the females. Moreover, we found that P2X4R KO mice carried the P2X7 receptor 451P wildtype allele, whereas the wildtype mice carried the 451L mutant allele. In conclusion, this study suggests that P2X4R could play a role in bone remodeling, but more importantly, it underlines the potential pitfalls when using knockout models and highlights the importance of interpreting results with great caution. Further studies are needed to verify any specific effects of P2X4R on bone metabolism.

     

Characterization of the growth plate-bone interphase region using cryo-FIB SEM 3D volume imaging

The interphase region at the base of the growth plate includes blood vessels, cells and mineralized tissues. In this region, cartilage is mineralized and replaced with bone. Blood vessel extremities permeate this space providing nutrients, oxygen and signaling factors. All these different components form a complex intertwined 3D structure. Here we use cryo-FIB SEM to elaborate this 3D structure without removing the water. As it is challenging to image mineralized and unmineralized tissues in a hydrated state, we provide technical details of the parameters used. We obtained two FIB SEM image stacks that show that the blood vessels are in intimate contact not only with cells, but in some locations also with mineralized tissues. There are abundant red blood cells at the extremities of the vessels. We also documented large multinucleated cells in contact with mineralized cartilage and possibly also with bone. We observed membrane bound mineralized particles in these cells, as well as in blood serum, but not in the hypertrophic chondrocytes. We confirm that there is an open pathway from the blood vessel extremities to the mineralizing cartilage. Based on the sparsity of the mineralized particles, we conclude that mainly ions in solution are used for mineralizing cartilage and bone, but these are augmented by the supply of mineralized particles.