机械刺激对体外骨髓基质干细胞骨向分化作用的研究进展

具有多向分化潜能的骨髓基质干细胞(BMSCs)为力学敏感细胞,在体外适当机械刺激作用下,其生物学特性会发生功能性改变,以达到力学刺激的最佳要求,并表现为成骨向分化。此过程涉及多条信号转导通路,但BMSCs如何将机械刺激转变为生物信号,进而指导体内骨形成和改建的确切机制仍不清楚。本文就机械刺激对体外骨髓基质干细胞骨向分化的影响及可能的作用机制等方面的研究进展作一综述。     

Two novel distinct COL1A2 mutations highlight the complexity of genotype–phenotype correlations in osteogenesis imperfecta and related connective tissue disorders

Osteogenesis imperfecta is a heritable connective tissue disorder characterized by variable symptoms including predisposition to fractures. Despite the identification of numerous mutations, a reliable genotype–phenotype correlation has remained notoriously difficult. We now describe two patients with osteogenesis imperfecta and novel, so far undescribed mutations in the COL1A2 gene, further highlighting this complexity. A 3-year-old patient presented with features reminiscent of a connective tissue disorder, with joint hypermobility, Wormian bones, streaky lucencies in the long bones and relative macrocephaly. The patient carried a heterozygous c.1316G > A (p.Gly439Asp) mutation in the COL1A2 gene located in a triple-helix region, in which glycine substitutions have been assumed to cause perinatal lethal OI (Sillence type II). A second family with type I osteogenesis imperfecta carried a heterozygous nonsense mutation c.4060C > T (p.Gln1354X) within the last exon of COL1A2. Whereas other heterozygous nonsense mutations in COL1A2 do not lead to a phenotype, in this case the mRNA is presumed to escape nonsense-mediated decay. Therefore the predicted COL1A2 propeptide lacks the last 13 C-terminal amino acids, suggesting that the OI phenotype results from decelerated assembly and overmodification of the collagen triple helix. The presented COL1A2 mutations exemplify the complexity of COL1A2 genotype–phenotype correlation in genetic counselling in OI.     

Clinical manifestations and dental management of dentinogenesis imperfecta associated with osteogenesis imperfecta: Case report

Dentinogenesis imperfecta (DI) associated with osteogenesis imperfecta (OI) is a genetic disorder that affects the connective tissues and results in dentine dysplasia. This case report discusses the systemic and dental manifestations of OI and DI in a 4-year-old child, with moderate presentation of both disorders, who was treated at King Fahd Military Medical Complex in Dhahran. Dental treatment included the use of strip and stainless-steel crowns under local anesthesia, as well as behavior modification techniques. Rigorous home care instructions, including reinforcement of the oral hygiene practice and avoidance of any episode that may lead to bone fracture, were discussed with the parents. The case was reevaluated at 3-month follow-up visits, wherein the medical and dental histories were updated, the child’s growth was monitored, periodic clinical and radiographic examinations were performed, and the oral hygiene was evaluated via the debris index score and caries risk assessment. Further treatment of the permanent dentition may be needed in the future.     

MAPKs通路在MSCs的增殖及向成骨细胞分化过程中的作用

间充质干细胞（MSCs）是一种多潜能成体干细胞,在体外诱导剂的作用下能向成骨细胞分化。在MSCs向成骨细胞分化过程中,受到MAPKs、BMPs、Notch和Wnt等多种信号通路的调控。其中MAPKs信号通路研究比较深入,近年来研究表明在MAPKs信号通路的五种途径中,ERKs、p38MAPK和JNKs途径参与了成骨细胞增殖和分化的信号转导。现对MAPKs通路与其参与的MSCs增殖和成骨分化过程简要综述。     

BONE-INDUCTIVE EFFICACY OF RECOMBINANT HUMAN BONE MORPHOGENETIC PROTEIN-2 EXPRESSED IN ESCHERICHIA COLI: AN EXPERIMENTAL STUDY IN RAT MANDIBULAR DEFECTS

Because to our knowledge the efficacy of prokaryotically expressed recombinant human bone morphogenetic proteins (rhBMP) to promote orthotopic osteogenesis has not previously been investigated, our aim was to test the efficacy of rhBMP-2 produced in Escherichia coli to promote bone healing in a standardised experimental bone healing model in rat mandibles. Different doses of rhBMP-2 were delivered in an absorbable collagen sponge carrier, and microporous barrier membranes were placed over half the number of defects in each treatment group, thereby making intraosseous cells the only recruitment source for new osteogenic cells. Results were evaluated by computerised image analysis after 12 and 24 days. The relative efficacy of rhBMP-2 preparations of different purity was also compared. E coli-produced rhBMP-2 stimulated bone healing, but its efficacy was estimated to be about one order of magnitude less than that of rhBMP-2 expressed in eukaryotic cells. We conclude that bacterially expressed rhBMP-2 is osteogenic in vivo, although higher doses will be required than of rhBMP-2 expressed in mammalian cell lines.     

成人型成骨不全症1例报告

正患者,女,56岁,因右髋部疼痛伴活动受限2个月余就诊。患者自诉2个月前无明显诱因出现右髋部疼痛,活动受限,不能久行、久立,休息后可缓解。10年前无明显外因出现双侧跟腱断裂;糖尿病史5年;否认外伤史。母亲及妹妹均患有成骨不全症。入院查体:体型矮小,营养尚可,神志清楚,表情自如,回答清楚,查体合作,身高1.55 m。全身皮肤黏膜未见明显异常,头发花白稀疏。巩膜深蓝色(图1a);     

磁性纳米粒子复合支架及外加磁场影响成骨作用的研究进展

磁性纳米粒子（MNP）具有独特的磁响应性、生物相容性,在作为生物材料时可通过其内在的微小磁场促进成骨分化。掺入MNP的磁性复合支架保留了MNP的超顺磁性,具有良好的物理机械性能以及生物学性能,在体内外均取得良好的成骨效果。外加磁场可通过影响细胞代谢行为促进骨组织修复,与MNP复合支架结合可起到协同促进骨组织修复再生的作用,在骨组织工程领域的应用潜力巨大。本文就MNP复合支架的性能、MNP复合支架和磁场的成骨作用研究进展作一综述,为MNP复合支架进一步研究和临床应用提供参考。     

动态监测骨代谢标志物在诊治强直性脊柱炎中的意义

目的通过对血清骨代谢指标的动态检测探讨其与强直性脊柱炎(AS)发生发展的相关性,为AS的诊断预后及治疗提供客观依据。方法根据AS患者骶髂关节的病损程度分早期、进展期、晚期3期,选择各50例门诊及住院患者。对照组选择年龄及性别相匹配的50名健康对照者,取患者晨起空腹血样,采用电化学发光免疫(ECLIA)及酶联免疫吸附试验(ELISA)检测骨代谢相关指标:甲状旁腺素(PTH),总Ⅰ型前胶原氨基末端(N端)前肽(tPINP),骨钙素N端中分子片段(N-MID OT),I型胶原C端肽(β-CTX),25-羟基维生素D3[25-(OH)D3],Ⅰ型胶原交联羧基末端肽(ICTP)。对3期各组间数据进行比较及相关分析。结果①AS组血清中NMID OT、25-(OH)D3低于健康对照组,β-CTX、ICTP高于健康对照组,组间比较差异均有统计学意义(P<0.01);tPINP、PTH浓度水平在AS患者组与健康对照组组间无显著差异性(P>0.05)。②AS晚期组血清中N-MID OT、25-(OH)D3低于早期组,组间比较差异具有统计学意义(P<0.05);晚期组β-CTX、ICTP浓度水平高于早期组,组间比较差异均有统计学意义(P<0.05);晚期组与早期组tPINP、PTH在组间差异无统计学意义(P>0.05);随着AS疾病的进展,血清中N-MID OT、25-(OH)D3浓度水平逐渐降低,β-CTX、ICTP浓度水平显著升高。结论血清骨代谢指标在分期不同的AS患者中存在异常,不同指标参与了AS的骨吸收及骨转换过程,可为AS的诊断预后及治疗提供客观依据。     

The synergetic effect of hydrogel stiffness and growth factor on osteogenic differentiation

Cells respond to various chemical signals as well as environmental aspects of the extracellular matrix (ECM) that may alter cellular structures and functions. Hence, better understanding of the mechanical stimuli of the matrix is essential for creating an adjuvant material that mimics the physiological environment to support cell growth and differentiation, and control the release of the growth factor. In this study, we utilized the property of transglutaminase cross-linked gelatin (TG-Gel), where modification of the mechanical properties of TG-Gel can be easily achieved by tuning the concentration of gelatin. Modifying one or more of the material parameters will result in changes of the cellular responses, including different phenotype-specific gene expressions and functional differentiations. In this study, stiffer TG-Gels itself facilitated focal contact formation and osteogenic differentiation while soft TG-Gel promoted cell proliferation. We also evaluated the interactions between a stimulating factor (i.e. BMP-2) and matrix rigidity on osteogenesis both in vitro and in vivo. The results presented in this study suggest that the interactions of chemical and physical factors in ECM scaffolds may work synergistically to enhance bone regeneration.     

Silicate bioceramics enhanced vascularization and osteogenesis through stimulating interactions between endothelia cells and bone marrow stromal cells

The facts that biomaterials affect the behavior of single type of cells have been widely accepted. However, the effects of biomaterials on cell–cell interactions have rarely been reported. Bone tissue engineering involves osteoblastic cells (OCs), endothelial cells (ECs) and the interactions between OCs and ECs. It has been reported that silicate biomaterials can stimulate osteogenic differentiation of OCs and vascularization of ECs. However, the effects of silicate biomaterials on the interactions between ECs and OCs during vascularization and osteogenesis have not been reported, which are critical for bone tissue regeneration in vivo. Therefore, this study aimed to investigate the effects of calcium silicate (CS) bioceramics on interactions between human umbilical vein endothelial cells (HUVECs) and human bone marrow stromal cells (HBMSCs) and on stimulation of vascularization and osteogenesis in vivo through combining co-cultures with CS containing scaffolds. Specifically, the effects of CS on the angiogenic growth factor VEGF, osteogenic growth factor BMP-2 and the cross-talks between VEGF and BMP-2 in the co-culture system were elucidated. Results showed that CS stimulated co-cultured HBMSCs (co-HBMSCs) to express VEGF and the VEGF activated its receptor KDR on co-cultured HUVECs (co-HUVECs), which was also up-regulated by CS. Then, BMP-2 and nitric oxide expression from the co-HUVECs were stimulated by CS and the former stimulated osteogenic differentiation of co-HBMSCs while the latter stimulated vascularization of co-HVUECs. Finally, the poly(lactic-co-glycolic acid)/CS composite scaffolds with the co-cultured HBMSCs and HUVECs significantly enhanced vascularization and osteogenic differentiation in vitro and in vivo, which indicates that it is a promising way to enhance bone regeneration by combining scaffolds containing silicate bioceramics and co-cultures of ECs and OCs.