基于FGFR1靶点分子虚拟对接筛选淫羊藿中抗骨质疏松的药效成分

目的基于FGFR1蛋白靶点筛选淫羊藿中抗骨质疏松的药效成分。方法采用维甲酸灌胃14 d复制大鼠骨质疏松模型,给予淫羊藿提取物进行干预;采用Western blotting法检测各组大鼠股骨FGFR1蛋白的表达,用UPLC-Q-TOF-MS确认提取物中化学成分。基于FGFR1靶点进行分子虚拟对接筛选药效成分。结果淫羊藿能够改善大鼠骨质疏松症状,并提高FGFR1蛋白的表达。淫羊藿提取物中指认出23种化合物,其中淫羊藿苷、淫羊藿次苷I、箭藿苷C可与FGFR1可以有效对接。结论淫羊藿中淫羊藿苷、淫羊藿次苷I、箭藿苷C可能通过上调FGFR1发挥抗骨质疏松作用。     

Morphofunctional status and osteogenic differentiation potential of human mesenchymal stromal precursor cells during <Emphasis Type="Italic">in vitro</Emphasis> modeling of microgravity effects

We studied the effects of long-term (20-day) simulated microgravity (clinostatic exposure) and osteogenic differentiation stimuli on cultured mesenchymal stromal precursor cells isolated from human bone marrow. Clinostatic exposure significantly reduced proliferative activity of mesenchymal stem cells in comparison with the static and dynamic control, increased the number of large flat cells in the culture, and stimulated migration activity of cells. Phenotypic studies of surface antigens (CD90, CD54, CD106, CD105, CD34, CD45, class 1 HLA) during clinostatic exposure of mesenchymal stem cell cultures showed differences in their expression between experimental and control groups. Studies of osteogenesis of precursor cell showed that cell differentiation potential can be directed towards osteogenesis by a combination of clinostatic exposure and differentiation stimuli. The results confirm gravity sensitivity of human bone marrow precursor cells and open new vistas for understanding of the mechanisms of bone tissue loss in humans under conditions of space mission.     

Management of the severe cleft and syndromic midface hypoplasia

Distraction Osteogenesis (DO) has become a treatment alternative to treat severe craniofacial skeletal dysplasias. A rigid external distraction (RED) device has been successfully used to advance the maxilla as well as the maxillary, orbital and forehead complex (monobloc) in children as young as two years, adolescents and adults. This approach has provided predictable and stable results. It can be applied by itself or as an adjunct to traditional orthognathic and craniofacial surgical procedures. The technical aspects, including planning, surgical and orthodontic procedures, required to properly apply the technique are presented. For this severe group of patients the technique has been found to be simpler and safer than traditional surgical methods. Maxillary and midfacial advancement through distraction has been found to be extremely stable in the patients in whom the technique was used. The reasons for stability are discussed as well as the observed morphologic changes in the facial soft tissues, velopharyngeal mechanism and airway. However, challenges remain to be solved to improve all distraction techniques and the need for collaboration between researchers and clinicians is emphasized to maximize the benefits of this already promising and rewarding approach.     

脂联素在衰老和损伤中成骨作用的研究进展及主要困惑探讨

脂肪因子脂联素与骨代谢关系密切,并进行了大量的细胞、模型动物及人群的调查研究。虽然许多研究证实了脂联素对成骨的正向调节作用,但是研究结果不完全一致。目前仍未能完全了解脂联素信号通路在年龄、疾病及骨修复中的重要性。该述评探讨了脂联素对成骨作用的初步研究结论,脂联素不同异构体、不同受体的可能作用通路,以及老年人群的脂联素生物学改变。探究脂联素对骨骼生物学的调控作用有助于药物开发和非药物（生活方式）干预方式的研究。针对脂联素信号进行干预,可能有助于维护衰老过程中的骨健康和损伤后的骨骼修复。     

3D细胞培养和类器官在骨髓源性间充质干细胞成骨分化中的研究进展

类器官（organoids）来源于自体的组织及干细胞,是通过体外3D培养后形成的细胞团块,这种团块具有原始组织及器官的三维结构,并保留了相对应的功能和遗传特征。由于其具有模拟特定机体器官的发育和疾病发生发展的潜能,这一模型在多种药物的筛选和分子机制研究中拥有更多的优势。近年来,已有实验表明骨髓源性间充质干细胞（BMSCs）通过3D培养及成骨分化可以形成骨的类器官,并可以植入机体发挥特定的作用。这种骨类器官模型的构建,不仅可以为骨质疏松等相关疾病研究提供更多方法,还在骨组织移植及修复等组织工程学中发挥重要作用。本文就BMSCs成骨分化的类器官相关3D模型研究进展作一综述,为BMSCs成骨分化的类器官的基础和临床研究提供更多理论依据和思路。     

雪旺细胞调控骨组织再生的研究进展北大核心CSCD

目的对雪旺细胞调控骨组织再生的研究进展进行综述。方法广泛查阅国内外雪旺细胞对组织再生研究的相关文献,从雪旺细胞的骨再生作用、多样化促进组织再生能力、旁分泌神经因子网络的营养效应和其在骨组织工程学中的应用等多个方面进行总结分析。结果作为周围神经系统的组成部分,雪旺细胞通过旁分泌效应,调控多种神经营养因子和生长因子的表达,从而有效参与到了血管和骨骼等非神经组织的再生分化过程,体现了其具有神经-血管-骨整合的营养效应。结论充分利用雪旺细胞的神经、血管和骨骼组织多能化再生效应,可为组织工程骨的临床应用提供新思路。     

Functionalized Polycaprolactone/Hydroxyapatite Composite Microspheres for Promoting Bone Consolidation in a Rat Distraction Osteogenesis Model

Distraction osteogenesis (DO) is an ideal model to study bone regeneration. The major limitation is the relatively long period required for new bone consolidation. Here, we investigated whether the application of polycaprolactone (PCL) and hydroxyapatite (HA) composite microspheres could enhance bone formation in DO. Pure PCL microspheres and composite PCL and 10% HA microspheres were synthesized. Bone mesenchymal stem cells isolated from green fluorescent protein rats (GFP-rBMSCs) were cultured with microspheres in a rotary bioreactor system. Scanning electron microscopy was used to examine the microstructures. Osteogenic differentiation of rBMSCs was confirmed. Moreover, PCL/HA (20 mg) and PCL (20 mg) were locally administered into the distraction gap in the rat DO model toward the end of the distraction period. Imaging detection, mechanical and histological examinations were performed to assess the quality of the 4-week regenerates. Results showed that the microspheres were of uniform size and monodisperse. After incubation with rBMSCs in culture, PCL/HA microspheres showed a better ability for cell adhesion and osteogenic differentiation compared with PCL microspheres. In vivo, bone volume/total tissue volume, bone mineral density, and mechanical properties of the new callus were significantly higher in the PCL/HA group compared with the PCL group. Histological analyses confirmed improved bone formation and vascularization in PCL/HA group. We presented an effective protocol for the generation of functionalized microspheres and demonstrated implantation of PCL/HA microspheres into the distraction regenerate could significantly enhance bone consolidation. Thus, the application of PCL/HA composite microspheres may be a novel approach for promoting bone regeneration. This article is protected by copyright. All rights reserved © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:961-971, 2020     

不同年龄段健康人群骨代谢指标Ⅰ型前胶原N末端前肽的特点分析

目的确定健康中国人群中Ⅰ型前胶原N末端前肽(type Ⅰ procollagen propeptide,PⅠNP)的年龄和性别特异性参考区间。方法采用骨密度测定法测定骨密度正常的中国人群599份血清,建立参考区间。年龄组分为20～29岁、30～39岁、40～49岁、50～59岁、≥60岁。结果在划分中国男性和女性人群的年龄组时,不同年龄组的总PINP存在显著差异。在男性人群中,PⅠNP水平随着年龄的增长而降低,然后在中年后保持稳定。在女性人群中,与男性人群相似的下降趋势与50～59岁年龄组的急剧增加相似。结论本研究初步建立了具有正常骨密度的中国男性和女性人群与年龄相关的PⅠNP参考区间。     

Cisplatin inhibits bone healing during distraction osteogenesis

Osteosarcoma (OS) is the most common malignant bone tumor affecting children and adolescents. Many patients are treated with a combination of chemotherapy, resection, and limb salvage protocols. Surgical reconstructions after tumor resection include structural allografts, non‐cemented endoprostheses, and distraction osteogenesis (DO), which require direct bone formation. Although cisplatin (CDP) is extensively used for OS chemotherapy, the effects on bone regeneration are not well studied. The effects of CDP on direct bone formation in DO were compared using two dosing regimens and both C57BL/6 (B6) and tumor necrosis factor receptor 1 knockout (TNFR1KO) mice, as CDP toxicity is associated with elevated TNF levels. Detailed evaluation of the five‐dose CDP regimen (2 mg/kg/day), demonstrated significant decreases in new bone formation in the DO gaps of CDP treated versus vehicle treated mice (p < 0.001). Further, no significant inhibitory effects from the five‐dose CDP regimen were observed in TNFR1KO mice. The two‐dose regimen significantly inhibited new bone formation in B6 mice. These results demonstrate that CDP has profound short term negative effects on the process of bone repair in DO. These data provide the mechanistic basis for modeling peri‐operative chemotherapy doses and schedules and may provide new opportunities to identify molecules that spare normal cells from the inhibitory effects of CDP. © 2013 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 32:464–470, 2014.     

New bone formation enhanced by ADSCs overexpressing hRunx2 during mandibular distraction osteogenesis in osteoporotic rabbits

Promoting new bone formation during distraction osteogenesis (DO) in elderly patients with osteoporosis is still a challenge. In this study, we investigated the effect of gene therapy using local Runt‐related gene 2 on new bone formation during osteoporotic mandibular DO in rabbits. First, we successfully established a mandibular osteoporotic animal model by ovariectomizing rabbits. Second, the right mandibles of the osteoporotic rabbits were distracted after corticotomy. The distraction gap of the rabbits in Group A2 and B2 were injected with Adv‐hRunx2‐GFP‐transfected adipose‐derived stromal cells (ADSCs) and Adv‐GFP‐transfected ADSCs, respectively. Rabbits in Groups C2 (ovariectomized control) and D2 (sham surgery control) were injected with physiologic saline. New‐generation bone tissue in the distraction gap was analyzed via plain radiographic examinations, micro‐computed tomography, histological examinations, and biomechanical testing at weeks 3, 6, and 9 of the consolidation period. Results of above examinations showed that no ideal new bone formation was observed in Groups B2 and C2, but obvious ideal new bone formation was observed in Group A2 and D2. The results suggested that gene therapy using rhRunx2‐modified ADSCs promoted new bone formation during osteoporotic mandibular DO and effectively compensated for the detrimental effects of systemic osteoporosis on new bone formation. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 32:709–720, 2014.