应力在肌腱愈合中的作用

背景：肌腱在体内作为承受机械负荷的组织,具有独特的生物力学特点,对其施加不同的应力时会改变它的结构和生物学反应,因此,适当的应力刺激对肌腱生长及愈合是必要的。 目的：全面了解损伤肌腱的愈合过程及生物力学属性,明确应力在肌腱愈合过程中作用的研究进展。 方法：电子检索中国生物医学文献数据库和计算机PubMed数据库1967年1月至2014年12月收录的应力对于肌腱愈合影响的相关综述和论文报告,并从微观和宏观层面进行分析应力在损伤肌腱愈合过程中的作用。 结果与结论：共纳入应力在肌腱愈合中的作用相关文献59篇。肌腱是对应力敏感的组织,对其施加不同的应力时会改变它的结构和生物学反应。适当的应力刺激对肌腱生长及愈合是必要的。如何在最低(引起异化作用)和最高应力负荷(会引起微创)之间达到一个很好的平衡是临床肌腱损伤愈合的难题。目前绝大多数肌腱损伤区域是以胶原为主要成分的纤维瘢痕组织愈合,肌腱损伤的治疗仍然是临床医生所面临的巨大挑战。   中国组织工程研究杂志出版内容重点：组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松;组织工程     

组织工程化肌腱在肌腱修复过程中的作用

目的：综述肌腱组织工程在肌腱修复过程中的应用进展。 方法：应用计算机检索1993-01/2009-10 PubMed数据库及维普数据库有关肌腱组织工程研究进展、肌腱支架材料生物力学分析、生物材料在肌腱组织工程中应用及组织工程技术在修复肌腱缺损临床应用方面的相关文献,英文检索词为“tendon transplantation,tissue engineering,biologicalmaterial,cell stent”,中文检索词为“肌腱移植,组织工程,生物材料,细胞支架”。检索文献量总计132篇。 结果：目前组织工程化肌腱的研究已经取得了显著的成果,但要真正应用于临床,大批量生产,仍存在一些问题。诸如最适的种子细胞来源、理想的支架材料、最佳的培养条件以及植入体内的检测方法等,在组织工程真正成为一种治疗肌腱缺损和功能重建的选择之前,这些问题都是有待进一步研究和解决的。 结论：要真正实现体外预制有生命的种植体完全替代人体组织、器官功能,尚面临着许多挑战。     

CD40L在树突状细胞成熟和发育过程中的作用

免疫反应的启动首先是由抗原递呈细胞（APC）捕获抗原，经过加工和处理后将抗原信息递呈给T、B淋巴细胞，继而引发一系列的特异性免疫应答．如免疫介导和免疫耐受。树突状细胞（DCs）是体内最重要的APC，其最大的特点是能够激活未致敏T细胞（Naive T cells）且功能强大，所以在免疫应答的诱导中具有独特的地位。     

可吸收生物材料在肌腱损伤重建中的防粘连作用

BACKGROUND: After sports tendon injury, tendon adhesion is the main reason for the failure to repair tendon injury. So, an ideal anti-adhesion material plays an important role in the tendon reconstruction.     

聚乳酸防粘连膜在肌腱修复中的应用

背景：如何使肌腱修复后少发生或不发生粘连,尽快实现其滑动功能又不影响肌腱本身的愈合？ 目的：观察聚乳酸防粘连膜在肌腱损伤修复后的防粘连效果。 方法：选择解放军南京军区南京总医院骨科收治的手部屈伸肌腱断裂患者60例(共95根肌腱),随机分为2组。生物防粘连膜组采用弘健医用膜包裹吻合口1.5~2.0 cm;对照组不使用生物防粘连膜。修复后6个月屈肌腱采用TAM系统评定,伸肌腱采用Miller分级法评定,比较其综合优良率。 结果与结论：修复后均随访达半年以上,生物防粘连膜组综合优良率为90%(45/50),高于对照组综合优良率67%(30/45)   (P < 0.05)。提示聚乳酸防粘连膜临床应用简单便捷,有效降低了肌腱修复后粘连的形成,临床疗效肯定。      

基因治疗在肌腱愈合中的应用

肌腱损伤修复后,常因肌腱粘连而导致功能障碍,这是目前尚未解决的一个难题。随着分子生物学理论的发展,人们对生物组织中部分基因的调控、表达和蛋白质的合成过程,以及在肌腱愈合过程中对肌腱的形态和生物力学特性的影响有了一定的认识[1]。对肌腱愈合机制的研究已经进入基因水平。本文就这方面的研究进展进行综述。1基因治疗概述基因治疗就是将外源基因导入靶细胞并有效表达,从而达到治疗疾病的目的。根据对宿主病变细胞基因采取的措施不同,基因治疗分为基因置换,基因修正,基因增量和基因失活。在基因治疗中,载体和转移方法是比较重要的两…     

一氧化氮在中枢神经系统发育中的作用

一氧化氮作为中枢神经系统内的非经典性细胞递质和信使分子,有着多方面的生物效应。在神经发育的过程中,一氧化氮可通过NO/cGMP系统调节突触的形成及修饰,介导成熟期突触可塑性等过程。本文结合其生物学特性和作用机制就一氧化氮对中枢神经系统发育的影响作一综述。     

MicroRNAs在心脏发育和疾病中的作用

微小RNA(microRNA,miRNA)是一种长度为18-24核苷酸单链的内源性非编码小RNA,在进化过程中高度保守,通过与靶基因序列特异性相互作用在转录后水平调节基因表达,参与多种生物学过程。最初发现的内源性miRNA是lin-4和let-7,它们通过与靶mRNA的3'端非翻译区(untranslated region,UTR)相结合而发挥负性调节作用。以往的研究表明,miRNA主要参与器官形成、造血、细胞增殖与凋亡、肿瘤生成等生物学过程,而最近一些研究发现,miRNAs参与调节心脏的生长发育、机械重构和电重构过程。现就miRNA在心脏中作用的最新研究进展进行综述。     

细胞因子在肌腱损伤修复中的研究进展

肌腱损伤后的粘连是手外科领域的难题之一 ,国内外不少学者对其进行了研究。结果表明肌腱愈合存在内源性愈合和外源性愈合两种机制[1] ,其中外源性愈合被认为是粘连发生的病理基础。因此 ,不少学者认为应设法抑制外源性愈合而促进内源性愈合。随着分子生物学的发展 ,细胞因子逐渐被学者们所认识并被证实其可调控细胞增殖分化 ,故在损伤修复中发挥着重要作用。在肌腱愈合中 ,相关细胞因子起关键的调控作用[2 ] 。在肌腱修复过程中 ,通过细胞因子调控细胞的增殖和基质合成来解决肌腱损伤修复和术后粘连是学者们感兴趣的课题之一。现就肌腱损伤…     

Angiogenesis Inhibitors Localized in Hypovascular Mesenchymal Tissues: Chondromodulin-I and Tenomodulin

The majority of mesenchymal tissues obtain their nutrients via a well-developed network of capillaries. Cartilage, however, is normally devoid of capillary networks and, with the exception of endochondral bone formation, is resistant to vascular invasion from surrounding tissues. However, because of its avascular nature, cartilage is widely regarded as an enriched source of endogenous angiogenesis inhibitors, and many previous attempts have been made to identify these factors. We have identified chondromodulin-I (ChM-I) as an angiogenesis inhibitor derived from extracts of fetal epiphyseal cartilage, based upon its growth inhibitory activity in vascular endothelial cells in vitro. In the musculoskeletal system, ChM-I is specifically expressed in the avascular zones of cartilage. Upon functional expression of human ChM-I precursor cDNA, the purified recombinant protein was found to block the growth of solid tumors by inhibiting angiogenesis. Recently, we also cloned a cDNA that encodes a novel type II transmembrane glycoprotein containing a cysteine rich C-terminal domain homologous to ChM-I. We termed this glycoprotein “tenomodulin” (TeM) after tendons that were found to be the predominant expression sites in addition to other dense connective tissues including ligaments and cornea. Subsequently, by employing an adenovirus-mediated expression system, we demonstrated that the ChM-I-like domain of TeM is both antiangiogenic and antitumorigenic. In this article, we summarize the structural characteristics and biological activities of these two antiangiogenic molecules.     

Tenomodulin variants, APOE and Alzheimer's disease in a Finnish case-control cohort

The tenomodulin gene (TNMD, locus Xq-22) encodes an angiogenesis inhibitor. It is an interesting candidate gene for Alzheimer's disease (AD), since it is expressed in brain, alterations in angiogenesis have been linked to AD and in our previous studies we have observed associations between TNMD and phenotypes, which are related to increased risk of AD. The common sequence variation in the TNMD was not associated with prevalence of AD among 526 cases and 672 controls. However, a significant interaction (p = 0.002) between rs5966709 and the APOE ε4-allele status was observed in women. Among the ε4-allele carriers, the women with rs5966709-TT genotype had smaller risk for having AD than those with other genotypes (odds ratio 0.47, p = 0.019, false discovery rate 10.4%). According to these results the sequence variation of TNMD is not associated with AD, but might modify the effect of APOE ε4-allele in women.     

Tenomodulin regulated the compartments of embryonic and early postnatal mouse masseter muscle

The masseter muscle (MM) is a complex tendinous laminar structure during development; however, the stage of the laminar structure formation is unknown. Tenomodulin (TeM) is a useful marker of tendons and has an anti-angiogenic cysteine-rich C-terminal domain. Therefore, we analyzed mRNA of TeM and angiogenesis markers (CD31 and vascular endothelial growth factor (VEGF)) and performed in situ hybridization for the TeM genes in MM from on embryonic day 12.5 (E12.5) to postnatal day 5 (P5). The TeM expression is at first detectable in the middle region of the mesenchymal connective tissue in the MM at E 12.5. The expression domains of the TeM during development typically include the middle region of the MM, particularly surrounding the vascular regions. The level of TeM mRNA in the MM increased from E12.5 to E17.5 and decreased after birth. In contrast, the levels of CD31 and VEGF mRNAs were almost constant from E12.5 to E18.5 and then low from birth onward. Therefore, the development of the laminar tendinous structure in the middle region between superficial and deeper regions of the MM first occurs during the process of tendon formation at embryonic day 12.5. In our study of MM development, the laminar structure regulating TeM also prevents vascular invasion during the formation of compartment of the MM. The tendon may relate to the components of muscle mass of MM.     

The role of movement in the development of a digital flexor tendon

D-tubocurarine was injected into the air sac of 8-day chick embryos to prevent movement of the digits of the hind limb. The embryos were paralyzed from the tenth to the eighteenth day, when the experiment was terminated. The immobilization of the flexor digitorum profundus tendons in the tarsus resulted in a loss of specialized structures around and on this tendon, as determined by light and electron microscopy. Specialized areas observed in the normal chick (synovial cavity, fibrocartilaginous area, and elastic vinculum) failed to form, as a result of the paralysis of the digit. Several authors have shown previously that movement is a requirement for the molding and maintenance of joint cavities in vivo, in ovo and in vitro (see text for references). We have shown that movement of the tendon is required to produce a functional tendon apparatus in the embryo and predict that movement is also required for regeneration after injury.     

The development of Golgi tendon organs

Summary The fine structural development of Golgi tendon organs (GTOs) was studied in leg muscles of the rat from day 18 gestation until 2 months after birth. Small axons were found at the aponeuroses on day 18, but GTOs were first identified on day 20–21 gestation. Prenatally, they appear as discrete islets in the aponeurosis in which a single Ib axon branches and terminates among fibroblasts, collagen bundles and on myotubes inserting into the tendinous tissue.The receptor body is formed during week 1 postnatal as a result of several concurrent processes: (1) New terminals arise and form numerous contacts with 5–9 myotubes inserting into the GTO area. The innervated myotube tips gradually recede from the aponeurosis. (2) Schwann cells and fibroblasts proliferate and form longitudinal strands adjoining the receding myotubes and converging towards the attachment to the aponeurosis. (3) Axonal branches ensheathed by Schwann cells form terminal enlargements and small-sized terminals. Terminal enlargements are predominantly filled with mitochondria, whereas their peripheral projections and small-sized terminals mainly contain clear and dense core vesicles. (4) Concomitantly collagen fibrils assemble between Schwann cell processes and the developing terminals, and interconnect with collagen bundles, linking the muscle fibre tips to the aponeurosis. Thus collagen bundles of the GTO, which eventually spiral around the terminals and bring about their depolarization when stretched, are formed concurrently with the developing terminals. (5) The GTO becomes encapsulated from day 2 postnatal onwards. (6) Axon terminals loosen their contacts with muscle fibres and are only found among collagen bundles of the receptor from day 5 postnatal onwards. (7) Muscle-fibre tips recede from the GTO lumen by day 7 after birth.Subsequently, the GTO grows further in length, acquires its fusiform shape by tightening of the capsule at both poles, and becomes structurally mature 2–3 weeks after birth.The Ib sensory axon together with Schwann cells appear to be the main formative agents in the GTO development, the Ib terminals presumably inducing the retraction of myotubes from the aponeurosis, and the Schwann cells affecting the assembly of collagen fibrils and bundles surrounding the terminals.     

The location-specific role of proteoglycans in the flexor carpi ulnaris tendon

Abstract

Tendons like the flexor carpi ulnaris (FCU) that contain region-specific distributions of proteoglycans (PGs) as a result of the heterogeneous, multi-axial loads they are subjected to in vivo provide valuable models for understanding structure–function relationships in connective tissues. However, the contributions of specific PGs to FCU tendon mechanical properties are unknown. Therefore, the objective of this study was to determine how the location-dependent, viscoelastic mechanical properties of the FCU tendon are impacted individually by PG-associated glycosaminoglycans (GAGs) and by two small leucine-rich proteoglycans (SLRPs), biglycan and decorin. Full length FCU tendons from biglycan- and decorin-null mice were compared to wild-type (WT) mice to evaluate the effects of specific SLRPs, while chondroitinase ABC digestion of isolated specimens removed from the tendon midsubstance was used to determine how chondroitin/dermatan sulfate (CS/DS) GAGs impact mechanics in mature FCU tendons. A novel combined genetic knockout/digestion technique also was employed to compare SLRP-null and WT tendons in the absence of CS/DS GAGs that may impact properties in the mature state. In all genotypes, mechanical properties in the FCU tendon midsubstance were not affected by GAG digestion. Full-length tendons exhibited complex, multi-axial deformation under tension that may be associated with their in vivo loading environment. Mechanical properties were adversely affected by the absence of biglycan, and a decreased modulus localized in the center of the tendon was measured. These results help elucidate the role that local alterations in PG levels may play in processes that adversely impact tendon functionality including injury and pathology.     

The role of graft materials in suture augmentation for tendon repairs and reattachment

Various biomaterials have been used to augment sutures for the repair and reattachment of tendons. This study examined four different graft materials in a simple and reproducible model using chicken Achilles tendons to determine the strength and mechanism of suture reinforcement of tendon repairs. The graft materials tested were Gore-Tex(R) Soft Tissue Patch, Graftjacket, bovine pericardium, and an experimental graft material from Xylos Corporation. Testing was performed in shear to simulate forces on a torn tendon repair and pull-off to simulate those on a tendon reattachment to bone. Compared to unaugmented suture, grafts increased suture fixation strength from 10% to 60% in shear and from 0% to 36% in pull-off with the bovine pericardium graft, providing significant improvement in both tests. In no cases (even unaugmented) did the suture pull directly through the tendon, but instead sliced along it, demonstrating that the interface between the suture and the tendon determines fixation strength. Grafts function by increasing the area, friction, and nature of this interface, not by acting as a barrier for suture pull-through.     

The role of patellar tendon morphometry on anterior knee pain

Purpose  

To investigate the morphometry of patellar tendon with magnetic resonance imaging (MRI) and to reveal the relation between patellar tendon properties and anterior knee pain (AnKP).     

The role of the non‐collagenous matrix in tendon function

Tendon consists of highly ordered type I collagen molecules that are grouped together to form subunits of increasing diameter. At each hierarchical level, the type I collagen is interspersed with a predominantly non‐collagenous matrix (NCM) (Connect. Tissue Res., 6 , 1978, 11). Whilst many studies have investigated the structure, organization and function of the collagenous matrix within tendon, relatively few have studied the non‐collagenous components. However, there is a growing body of research suggesting the NCM plays an important role within tendon; adaptations to this matrix may confer the specific properties required by tendons with different functions. Furthermore, age‐related alterations to non‐collagenous proteins have been identified, which may affect tendon resistance to injury. This review focuses on the NCM within the tensional region of developing and mature tendon, discussing the current knowledge and identifying areas that require further study to fully understand structure–function relationships within tendon. This information will aid in the development of appropriate techniques for tendon injury prevention and treatment.     

The development of fibrocartilage in the elastic tendon of the chicken wing

The elastic tendon of the chicken wing has five morphologically distinct regions. One of these regions is a distally located fibrocartilage from which fibrous connections extend to the capsule of the distal radius. In adult birds, this region shows the characteristics of a tendon-compressed fibrocartilage, with an accumulation of proteoglycans between thick collagen bundles arranged in a basket-weave formation. Here we study the development of this fibrocartilage in order to of compare it with other tendon fibrocartilages and try to identify the factors involved in fibrocartilage differentiation. This fibrocartilage initially developed by cell enlargement and accumulation of vimentin, with simultaneous deposition of proteoglycans in the extracellular matrix and an increase in the amount and thickness of collagen bundles. Elastic fibers were minor components associated with the collagen bundles. Cells could be classified into two main types. One was typically fibrocartilaginous and the other was fibroblast-like, the latter occurring in close association with the collagen bundles. These results establish the steps in the development of the elastic tendon fibrocartilage and provide a basis for future studies.