Using animal models in osteoarthritis biomarker research

Osteoarthritis (OA) is a disease that commonly affects human and veterinary patients. Animal models are routinely used for OA research, and the dog is a nearly ideal species for translational investigation of human OA biomarkers. The cytokine, chemokine, and matrix metalloprotease (MMP) profiles of synovial fluid, serum, and urine from dogs with surgically induced and naturally occurring OA were compared with dogs without OA using xMAP technology (Qiagen Inc., Valencia, CA). Markers that exhibited significant differences between groups were identified (monocyte chemoattractant protein 1 [MCP1], interleukin 8 [IL8], keratinocyte-derived chemoattractant [KC], and MMP2 and MMP3), and their sensitivities and specificities were calculated to determine their diagnostic usefulness in a future biomarker panel. Synovial fluid IL8 was the most sensitive, but MCP1 was also highly sensitive and specific. The alterations in KC suggested that it may differentiate between cruciate disease and other types of OA, and the MMPs were most sensitive and specific in the serum. This study provided additional insight to the participation of cytokines, chemokines, and MMPs in OA, and potential diagnostic biomarker candidates were identified. A brief literature review of other biomarker candidates previously examined using animal models is discussed.     

Angiogenesis in two animal models of osteoarthritis

OBJECTIVE: We have previously described angiogenesis at the osteochondral junction and in synovium of knees from patients with osteoarthritis (OA), but little is known about how closely animal models of OA resemble human disease with respect to vascular growth. This study aimed to characterise two animal models of knee OA with particular respect to osteochondral and synovial angiogenesis. METHOD: We examined the spontaneous Dunkin-Hartley (DH) guinea pig and medial meniscal transection (MNX) rat models of OA. Vessels at the osteochondral junction and in the synovium were identified by lectin immunohistochemistry and quantified by computer-assisted image analysis. Disease severity was assessed using a scoring system. RESULTS: Blood vessels crossed the osteochondral junction in juvenile rats and guinea pigs, with higher densities in the lateral than medial tibial plateau, the number decreasing with maturation in the absence of other OA changes. In the rat model, increased vascular density was observed both at the osteochondral junction and in the synovium, whilst osteochondral vascularity in control rats decreased with maturation, OA rats showed a persistence of blood vessels at the osteochondral junction. In rat synovium, blood vessel fractional area was increased in the hypertrophied synovium 14 days after surgery, then decreased to control levels by day 28. Significant differences in vascularity were not observed between affected (medial) and spared (lateral) compartments of guinea pig knees. CONCLUSION: The rat meniscal transection model of OA reproducibly displays both osteochondral and synovial angiogenesis comparable to our previous observations in human knee OA. DH guinea pigs, by contrast, display low vascularity throughout their protracted course of OA development. Changes in vascularisation occur early during the development of OA in the rat, and may contribute to the pathogenesis of OA.     

脊柱小关节骨关节炎动物模型的研究进展

腰痛是一种常见的疾病症状,影响人们的正常生活。大约有2/3的人一生中会受到腰痛的困扰。临床上引起腰痛的病因包括腰部肌肉劳损、腰椎间盘退变、腰椎小关节骨关节炎等。其中腰椎小关节骨关节炎被认为是腰痛的常见病因之一。据报告,15%～45%的腰痛患者是由脊柱小关节退变引起的。脊柱小关节又称为关节突关节,在脊柱中与椎间盘构成“三关节复合体”,是脊柱中唯一的滑膜关节。脊柱小关节包括关节面、关节腔、关节囊等结构,在脊柱后部承重中起着重要作用,同时参与脊柱屈伸和旋转运动。目前对于脊柱小关节骨关节炎的研究主要集中在动物模型研究上,通过动物模型模拟脊柱小关节骨关节炎疾病的发生发展。动物模型是研究脊柱骨关节炎疾病的重要工具之一。笔者就目前脊柱小关节骨关节炎动物模型研究进展情况综述如下。     

Preclinical animal models in trauma research

Preclinical modeling of human disease with animals has not been standardized for many common pathologic processes. Assorted animal models are being used to investigate the pathogenesis, prevention, and treatment of disease processes. Certainly it is difficult to interpret the current literature because there are diverse and often irrelevant models being implemented. Some models are used for reasons of size or ease rather than the true modeling of a physiological process. Application to granting agencies and design of animal studies is difficult without standardization of the ideal preclinical model for disease states. The current article addresses the preclinical animal modeling of osteoporosis, infection, bone defects, and cartilage injury. This article is a discussion of the current literature, commonly used models, and suggests preferred preclinical models for future research design.     

Ethical use of animal models in musculoskeletal research

The use of animals in research is under increasing scrutiny from the general public, funding agencies, and regulatory authorities. Our ability to continue to perform in‐vivo studies in laboratory animals will be critically determined by how researchers respond to this new reality. This Perspectives article summarizes recent and ongoing initiatives within ORS and allied organizations to ensure that musculoskeletal research is performed to the highest ethical standards. It goes on to present an overview of the practical application of the 3Rs (reduction, refinement, and replacement) into experimental design and execution, and discusses recent guidance with regard to improvements in the way in which animal data are reported in publications. The overarching goal of this review is to challenge the status quo, to highlight the absolute interdependence between animal welfare and rigorous science, and to provide practical recommendations and resources to allow clinicians and scientists to optimize the ways in which they undertake preclinical studies involving animals. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:740–751, 2017.

     

Reliability of rodent animal models in biomedical research

Despite the discrepancies observed between the data generated from humans and animals, it is a usual practice that the results obtained from animal models are extrapolated on humans. This review stresses that while animal models are essential for the research and development, a critical caution needs to be practiced in interpreting the results. Uncritical reliance on the results of animal experimentation can be dangerously misleading and has resulted in damages to human health in several cases. This review also discusses the role of certain confounding factors in using animal models due to which appropriate precautions need to be taken while deciding to conduct a study using animal models and caution is warranted in extrapolating the data obtained from pre-clinical studies on humans.     

Characteristics and impact of animal models used for sports medicine research

Animal models are commonly used for translational research despite evidence that the methodology of these studies is often inconsistent and substandard. This study describes the characteristics and impact of published research using animal models in the American Journal of Sports Medicine (AJSM).Peer-reviewed articles published in the AJSM between January 1990 and January 2010 using animal models were identified using MEDLINE. The articles were reviewed for funding source, anesthesia used, animal used, study type, study location, outcome measures, number of animals, duration of animal survival, main topic being studied, and positive or negative treatment effect. The impact factor of the studies published between 2005 and 2010 was calculated. Two hundred fifty-seven articles, or 6% (257/4278) of the total publications during the 20-year period, were analyzed. The impact factor increased from 1.83 in 2005 to 3.9 in 2010. The most common animals used were rabbits (24%) and pigs (16%). The anterior cruciate ligament was studied in 34% of the articles, and a pig model was used for 31% of these studies. Eighty-six percent of the studies had a positive treatment effect.This study shows that animal models used in sports medicine research lack uniformity in their methods and suggests that a publication bias may exist for animal research in the sports medicine literature.     

胆石症动物模型的应用与研究进展

胆石症动物模型已经成为在胆石病病因、预防、诊断和治疗等方面开展研究的重要平台和工具.由于胆结石的形成与肝胆系统结构功能异常、脂代谢失衡和免疫功能障碍的关系日益受到关注,因此学者们利用胆石症动物模型在上述领域的研究逐渐增多.近年来,模型动物对胆结石的遗传易感性也引起广泛研究兴趣.国内学者还利用胆石症动物模型进行中医药防治胆石病的探索.此外,建立大动物胆石症模型并应用于侵入性和有创性研究的成果也屡有报道.随着科技进步和研究的需要,将有更多适于胆石病研究的动物模型得以建立并被广泛应用.     

关节内注射富含血小板血浆在兔膝骨关节炎动物模型中的作用

目的评估关节内注射富含血小板血浆(PRP)对胶原酶诱导的兔膝骨关节炎(OA)动物模型的影响。方法 20只新西兰大白兔在超声引导下行右侧膝关节内胶原酶注射,建立兔OA动物模型。实验的第4周随机分为PRP组和生理盐水组,每组10只,每周给药1次,共4次。实验第9周取关节软骨观察软骨总体形态及软骨微形态的变化。结果 PRP组软骨总体形态评分为(1.7±0.3)分,明显低于生理盐水组的(3.5±0.6),分,差异有统计学意义(P0.05),提示PRP组软骨总体形态损伤较小;PRP组软骨微形态评分为(3.2±1.0)分,明显低于生理盐水组的(7.4±1.2)分,差异有统计学意义(P0.05),提示PRP组软骨微形态损伤较小。结论关节内注射PRP有保护软骨作用。     

Chemokines and inflammation in osteoarthritis: Insights from patients and animal models

Evidence has been building that the pathologic drive for development of osteoarthritis (OA) involves more than simple mechanical “wear and tear.” Inflammatory mechanisms play an important role in the tissue response to joint injury, and are involved in development of post‐traumatic OA. Inflammation also appears integral to the progression of OA, whether post‐traumatic or spontaneous, contributing to the evolution of joint tissue degradation and remodeling as well as joint pain. Both patient‐based studies and in vivo models of disease have shed light on a number of inflammatory pathways and mediators that impact various aspects of this disease, both structurally and symptomatically. Recent work in this field has implicated inflammatory chemokines in osteoarthritis pathogenesis. Expression of multiple chemokines and their receptors is modulated during disease in both patients and animal models. Although best known for their effects on leukocyte migration and trafficking within the immune system, chemokines can have a wide variety of effects on both motile and non‐motile cell types, impacting proliferation, differentiation, and activation of cellular responses. Their role in OA models has also demonstrated diverse effects on disease that exemplify their wide‐ranging effects. Understanding how these important mediators of inflammation impact joint disease, and whether they can be targeted therapeutically, is actively being investigated by many groups in this field. This narrative review focuses on evidence published within the last 5 years highlighting chemokine‐mediated pathways with mechanistic involvement in osteoarthritis and joint tissue repair. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:735–739, 2017.

     

Critical overview of all available animal models for abdominal wall hernia research

Purpose

Since the introduction of the first prosthetic mesh for abdominal hernia repair, there has been a search for the “ideal mesh.” The use of preclinical or animal models for assessment of necessary characteristics of new and existing meshes is an indispensable part of hernia research. Unfortunately, in our experience there is a lack of consensus among different research groups on which model to use. Therefore, we hypothesized that there is a lack of comparability within published animal research on hernia surgery due to wide range in experimental setup among different research groups.

Methods

A systematic search of the literature was performed to provide a complete overview of all animal models published between 2000 and 2014. Relevant parameters on model characteristics and outcome measurement were scored on a standardized scoring sheet.

Results

Due to the wide range in different animals used, ranging from large animal models like pigs to rodents, we decided to limit the study to 168 articles concerning rat models. Within these rat models, we found wide range of baseline animal characteristics, operation techniques, and outcome measurements. Making reliable comparison of results among these studies is impossible.

Conclusion

There is a lack of comparability among experimental hernia research, limiting the impact of this experimental research. We therefore propose the establishment of guidelines for experimental hernia research by the EHS.

     

Contribution of animal models to the research of the causes of diabetes

In most publications, animal models of diabetes have mainly been investigated for their multiple etiologies as well as for changes leading to diabetes and their genetic derivation. Aspects which seem important and need a special research endeavor are the mechanism of the causes of diabetes and the lapse into complications in different species, their molecular basis and possible arrest and prevention. A concise list and and short discussion of the intensively studied rodents is presented of spontaneous or nutritional background causing Type 2 diabetes but omitting diabetes evoked by transgenic manipulations or gene knockout techniques.     

结直肠癌肝转移的啮齿动物模型建立的研究进展

50％～ 60％的Ⅱ～Ⅲ期结直肠癌患者发生了肝转移,如何改善结直肠癌肝转移患者的预后是近年来国际上的研究热点.通过建立结直肠癌肝转移的动物模型是研究肿瘤细胞如何形成肝转移的理想手段.理想的结直肠癌肝转移动物模型应该可以完全模仿肿瘤细胞在人体中转移的过程,包括细胞学行为的改变及肿瘤生物学的发展.此外,此模型应该是可实现的、有肿瘤警示意义及符合伦理规范的.至今,仍没有一个理想模型可以完全符合上述所有条件.本综述主要分析对比各结直肠癌肝转移啮齿动物模型建立的优缺点.     

骨质疏松动物模型及其评价方法的研究进展*

骨质疏松动物模型,是研究骨质疏松病理和抗骨质疏松药物作用机理的重要依据。本文详细地论述了 4种骨质疏松动物模型的特点及原理:即(1)激素干预型骨质疏松动物模型,包括去势骨质疏松模型、甲状旁腺切除诱发的骨质疏松模型、下丘脑垂体缺陷诱发的骨质疏松模型、糖皮质激素诱导的骨质疏松模型和布舍瑞林诱发的骨质疏松模型等;(2)废用型骨质疏松动物模型,包括单侧肢体废用性模型、悬吊模型、钢板或螺钉内固定未骨折的骨骼诱发的骨质疏松模型、套筒法诱导大鼠骨质疏松模型和石膏绷带固定诱导骨质疏松模型等;（3)营养型骨质疏松模型,包括低钙饮食诱发的骨质疏松动物模型、低钠诱导的骨质疏松模型;（4)其它类型骨质疏松动物模型,包括维甲酸诱发的骨质疏松模型、链脲佐菌素诱发的骨质疏松模型、基因工程法诱导和联合造模法诱发的骨质疏松模型等。骨质疏松模型常见的评价包括密度测定法、生物化学指标法、骨形态学法和生物力学法等。衡量一种模型成功与否,必须将4种不同的指标评价方法结合起来进行综合评价,才能为基础和临床研究提供坚实的科学依据。     

酒精性急性胰腺炎的动物模型研究进展

酒精性急性胰腺炎（AAP）是目前仅次于胆源性急性胰腺炎（ABP）最严重的急性胰腺炎（AP）类型,其病情更重、病死率更高,多器官损害更明显。有研究表明,酒精使发生重症急性胰腺炎（SAP）的危险度增加,AAP较ABP易发展成SAP。近年来AAP相关研究正成为热点,获得理想动物模型有助于深入研究AAP的发病机制,而目前针对AAP研究构建有效的动物模型方法却十分欠缺。故笔者就国内外AAP动物模型研究方法进行综述,以期为AAP研究提供新思路。     

Laser photobiomodulation for cartilage defect in animal models of knee osteoarthritis: a systematic review and meta-analysis

Lasers in Medical Science - To review and assess the efficacy of laser photobiomodulation for cartilage defect in animal models of knee osteoarthritis (KOA). Medline, Web of Science, and EMBASE...