关节软骨力学特征研究进展

骨关节炎(osteoarthritis OA)是一种以关节疼痛和僵硬为特征的慢性退行性关节疾患,好发于老年人群。OA发病缓慢,病程较长,早期临床表现和组织学改变均不明显,限制了疾病的早期诊断与治疗。关节软骨微观结构决定了软骨宏观力学特性。软骨微观结构具有区域差异性,导致软骨的力学性能也具有区域依赖性,从软骨浅表区到深区软骨抗负荷、抗形变能力逐渐增加。然而,在OA病程发展过程中,软骨微观构成改变导致OA软骨抗负荷、抗形变能力降低。通过检测关节软骨的微观构成可以推测软骨的力学特性,反之检测软骨的力学指标可以了解软骨早期的微观改变,从而有助于了解OA的病程发展,便于疾病的早期诊断。综述近年来关节软骨在正常和急慢性损伤状态下力学性能的相关研究文献,阐述软骨结构与力学性能之间的关系,为OA的病程发展、早期诊断与治疗提供进一步理论依据。     

骨性关节炎软骨下骨病变机制研究进展

长期以来对骨性关节炎(osteoarthritis,OA)中关节软骨的改变进行较为深入的研究,但对软骨下骨的改变研究相对较少,而软骨下骨的改变是OA进程中所必需的病理变化.近年研究发现软骨下骨改变在OA发病过程中起着积极作用,软骨下骨硬化或软化不仅是OA发生的结果,而且与其发生发展密切相关,提示OA治疗既应关注软骨变化,又要预防软骨下骨退变.该文从软骨下骨的生物力学、骨重塑、分子生物学等方面就软骨下骨在骨性关节炎发病中的病变机制研究进展作一综述.     

甲状软骨、环状软骨和关节软骨的钙化

关节软骨和喉软骨随年龄增长,部分软骨经历了软骨内钙化,其确切的自然过程、衰老程度和衰老模式一直备受临床关注.在此过程中可能发生了喉软骨组织替代变化.然而年龄和喉结构组织变化之间缺乏高关联暗示其他不知因素影响关节软骨的变化,如病理因素、营养、激素和物理应力或遗传因素,都可能参与了软骨变化的进程.诸多因素的影响导致了在年龄...     

miR-140在软骨分化与骨关节炎的研究进展

骨关节炎(OA)是以关节软骨退行性变,关节内滑膜炎症以及周围关节和软骨下骨改变为特征的一种疾病。在OA组织中可观察到软骨细胞凋亡的分子特征,这表明软骨细胞的死亡在OA的发病机制中发挥关键作用。因此,对软骨分化的调控在延缓OA的发展中起到了至关重要的作用。miR-140在关节软骨中特异表达。越来越多的证据表明,miR-140通过抑制转录后水平的基因表达,在软骨细胞分化与OA中发挥重要分子作用。研究miR-140可为发现OA机制及治疗新靶点提供新的借鉴。     

软骨下骨量变化与软骨退变的相关性

背景：关节软骨与软骨下骨在骨关节炎病变进程中的相互作用机制目前尚未完全阐明。软骨下骨量改变在骨关节炎病理进程中亦发挥重要作用。 目的：分析2种手术方式及2种蛋白酶诱导建立兔膝关节骨关节炎动物模型的效果,以及软骨下骨量变化与关节软骨退变的相关性。 方法：32只新西兰大白兔随机分为4组：Hulth模型组、前交叉韧带切断模型组、Ⅱ型胶原蛋白酶组及木瓜蛋白酶组,每组8只,右膝关节造模,左膝关节作为自身对照。造模后0,4,8周行DXA扫描,8周行MRI扫描后处死实验动物,取双侧膝关节制作病理组织学切片,比较各组膝关节影像学表现、大体形态及病理变化,并采用Mankin评分进行定量分析。 结果与结论：造模后0,4,8周实验侧膝关节骨密度进行性降低,骨量降低程度Hulth模型组>前交叉韧带切断模型组>Ⅱ型胶原蛋白酶组>木瓜蛋白酶组。MRI显示实验侧股骨内外髁关节软骨厚度变薄,厚度Hulth模型组<前交叉韧带切断模型组<Ⅱ型胶原蛋白酶组<木瓜蛋白酶组。大体标本、组织切片观察及Mankin评分显示手术建模组骨关节炎程度较药物组重,Hulth模型组病变最重,木瓜蛋白酶组最轻。结果说明关节内手术及关节腔内注射蛋白酶均能建立骨关节炎动物模型;手术造模可复制出中晚期骨关节炎,药物诱导可产生骨关节炎早期改变。骨关节炎病变严重程度与软骨下骨骨密度呈负相关;关节软骨退变和软骨下骨改变相互关联,病变进行性发展。     

关节软骨生物力学与力学生物学 2022 年研究进展

关节软骨是动关节内骨表面具有弹性的负重结缔组织,能提供低磨损润滑、缓冲震荡、传递载荷等支撑作用,具有层级纤维复合结构和优异的力学性能。软骨内没有血管、神经和淋巴,代谢缓慢,损伤后难以实现自我修复。目前,高发的关节炎疾病仍是基础与临床研究的一大热点。关节软骨是力学敏感组织,力学环境影响着组织不同方向的发展。2022年,学者们继续对关节软骨的生物力学与力学生物学开展大量研究;对软骨形态、功能与力学状态,以及不同条件下软骨力学状态的研究报道较多;研究设计了一些软骨相关的动物、组织及细胞水平的加载装置,也开展了体外及在体力学载荷下软骨退变、损伤的修复研究,获得了重要的修复方法及手段。关节软骨的生物力学与力学生物学研究是关节炎、软骨缺损及修复的基础,关节软骨损伤修复定量力学条件的影响还需体内和体外深入研究。     

血管内皮生长因子在骨关节炎软骨钙化层重构中的作用

骨关节炎(OA)是一种以关节软骨退变、滑膜炎、软骨下骨改变及骨赘形成为病变基础的疾病。研究发现血管内皮生长因子(VEGF)参与了OA的发生发展过程,尤其是参与软骨钙化层重构;血清VEGF水平与关节炎严重程度密切相关。本文对此研究进展作一综述。     

软骨干/祖细胞修复软骨损伤的研究进展

关节软骨损伤是临床常见的运动损伤,然而关节软骨缺乏血管、神经支配,损伤后难以自身完全再生修复,缺乏有效的治疗会导致骨关节炎(OA)的发生。随着组织工程学的发展,近期研究发现,软骨组织中存在具有多向分化潜能的软骨干/祖细胞(CSPC),可以分化成高度同质化的软骨细胞。这种细胞在软骨损伤后自发迁移并参与软骨损伤组织修复和再生,有望成为治疗软骨损伤的新方法。本文对CSPC的分布、特征及其在软骨损伤和OA中的作用和应用进行综述,旨在为CSPC的研究应用及软骨损伤的治疗提供理论基础,为临床上治疗软骨损伤开拓新方向。     

关节软骨表面粗糙度对载荷响应的实验研究EI北大核心CSCD

软骨表面纤维化是骨关节炎的早期迹象,软骨表面损伤与载荷密切相关。本文目的是研究软骨表面粗糙度与载荷之间的关系,通过对新鲜的猪关节软骨施加冲击、压缩、疲劳载荷,每次间隔10 min测量软骨表面粗糙度数值,获得粗糙度在加载前后的变化规律。实验发现,载荷使软骨表面粗糙度增大,增大的数值与载荷大小相关,粗糙度恢复到初始情况的时间与载荷类型和载荷大小相关,冲击载荷对软骨表面粗糙度影响最大,其次是重度疲劳载荷、压缩载荷和轻度疲劳载荷。本文为揭示早期骨关节炎的发病机制和防治关节软骨疾病提供了参考数据。     

关节软骨润滑机制理论及仿生软骨材料的摩擦学应用

背景：关节软骨拥有着自然界中已知最有效的润滑,如膝关节和髋关节等,在生理性高压下,其表面摩擦系数低至0.001,如此低的摩擦对于关节正常活动来说非常必要。而软骨一旦发生退化,便易发生骨关节炎,因此探究软骨表面如此高效的润滑机制便显得尤为重要。同时,随着对关节润滑机制研究的深入,仿生软骨材料的飞速发展也为关节软骨之间的润滑及软骨损伤后的治疗带来了希望。目的：探讨关节软骨润滑机制以及仿生软骨材料摩擦学最新研究进展。方法：采用计算机检索中国知网、PubMed、Semantic Scholar、ScienceDirect和Wiley Online Library数据库中有关关节软骨润滑机制和仿生软骨材料的相关研究资料,根据纳入和排除标准,最终共选取60篇文献进行综述。结果与结论：(1)关节软骨的润滑并不是通过单一的机制,而是多种机制共同参与并实现高效润滑。(2)目前软骨润滑机制的主要研究聚焦于边界润滑以及水合润滑。(3)软骨润滑的边界润滑机制模型主要通过透明质酸、润滑素和磷酸酰胆碱等边界分子实现。(4)软骨间多重分子通过协同作用促进软骨润滑,这也为仿生软骨材料的设计提供了一种新思路。(5)用于...     

软骨下骨病理骨重建过程中骨细胞的代谢机制

背景：骨性关节炎一直被认为是关节软骨的退变和降解。现已逐步认识到软骨下骨结构及分子代谢的病理变化在关节退变的过程中发挥了重要的作用。 目的：观察软骨下骨在骨性关节炎进程中结构及细胞、相关因子和信号通道的变化,分析软骨下骨的病理改变对关节软骨退变的影响。 方法：使用骨性关节炎、软骨下骨、软骨退变、骨重建、骨代谢等关键词,检索中国知识资源总库与PubMed、Medline、Embase数据库中的相关研究论文,了解骨性关节炎进程中软骨下骨骨代谢平衡破坏后在结构及分子信号机制的病理变化,分析这些病理改变与关节软骨退变的关系。 结果与结论：纳入 54篇符合标准的文献。软骨下骨的病理骨重建贯穿骨性关节炎的始终,局部骨细胞的代谢及干细胞分化异常与软骨退变相互影响。通过对软骨下骨病理骨重建过程中骨细胞代谢机制的深入了解,为骨性关节炎提供了新的治疗靶点。     

Bone density of the human talus does not increase with the cartilage degeneration score.

Osteoarthritis (OA) is a common, disabling condition of synovial joints that can eventually lead to reduced, or lost, mobility. It is characterized by both articular cartilage degeneration and subchondral bone changes. However, a cause-and-effect relationship between the two tissues remains controversial. Increased subchondral bone density has been associated with early degenerative changes in the cartilage of knee, hip, and finger joints-joints in which progressive changes to OA are common. In contrast, the ankle joint is known to exhibit early cartilage changes, but is not prone to the development of OA. In the present study, it was found that cartilage degeneration on the talus is not associated with an increase in bone density, as assessed through peripheral quantitative computed tomography (pQCT).     

Bone density of the human talus does not increase with the cartilage degeneration score

Osteoarthritis (OA) is a common, disabling condition of synovial joints that can eventually lead to reduced, or lost, mobility. It is characterized by both articular cartilage degeneration and subchondral bone changes. However, a cause‐and‐effect relationship between the two tissues remains controversial. Increased subchondral bone density has been associated with early degenerative changes in the cartilage of knee, hip, and finger joints—joints in which progressive changes to OA are common. In contrast, the ankle joint is known to exhibit early cartilage changes, but is not prone to the development of OA. In the present study, it was found that cartilage degeneration on the talus is not associated with an increase in bone density, as assessed through peripheral quantitative computed tomography (pQCT). Anat Rec 266:81–86, 2002. © 2002 Wiley‐Liss, Inc.     

Relationship among biomechanical, biochemical, and cellular changes associated with osteoarthritis

Articular cartilage that lines the surface of long bones is a multilayered material. The superficial layer consists of collagen fibrils and chondrocytes that run parallel to the joint surface. In the deeper layers, the collagen fibrils are more randomly arranged and support vertical units termed chondrons containing rows of chondrocytes. In the deepest layers, the collagen fibrils run almost vertically and ultimately insert into the underlying subchondral bone. Osteoarthritis (OA) is a disease that affects articular cartilage and is characterized by enzymatic and mechanical breakdown of the extracellular matrix, leading to cartilage degeneration, exposure of subchondral bone, pain, and limited joint motion. Changes in mechanical properties of articular cartilage associated with OA include decreases in modulus and ultimate tensile strength. These changes parallel the changes observed after enzymatic degradation of either collagen or proteoglycans in cartilage. Results of recent viscoelastic studies on articular cartilage suggest that the elastic modulus of collagen and fibril lengths decrease in OA and are associated with a loss of the superficial zone and a decreased ability of articular cartilage to store elastic energy during locomotion. It is suggested that osteoarthritic changes to cartilage involve enzymatic degradation of matrix components and fibril fragmentation that is promoted by subsequent mechanical loading.     

Ultrastructural change of the subchondral bone increases the severity of cartilage damage in osteoporotic osteoarthritis of the knee in rabbits

Osteoporotic osteoarthritis is a phenotype of osteoarthritis (OA) manifested as fragile and osteoporotic subchondral bone. However, the ultrastructural features of subchondral bone in osteoporosis OA have not been determined. The study was aimed to investigate the ultrastructural dynamic changes of subchondral bone in osteoporotic OA model and how the ultrastructural damage in the subchondral bone caused by osteoporosis deteriorated the cartilage damage in OA. Eighteen rabbits were equally randomized to three groups, including the control, the OA and the osteoporotic OA groups. The structural changes of cartilage were evaluated by HE and safranin-O fast green staining, the Mankin’s grading system was used to assess the stage of OA progression. And microstructural or ultrastructural changes in subchondral bone were assessed by micro-computed tomography or by scanning electron microscopy. According to the changes of cartilage histopathology, the OA group was in the early pathological stage of OA while the osteoporotic OA group was in the middle stage of OA based on Mankin’s grading system. In addition, the damage of cartilage surface, reduction in the number of chondrocytes and the matrix staining were more increased in the osteoporotic OA group compared to the OA group. Compared to the OA group, the subchondral bone in the microstructure and ultrastructure in the osteoporotic OA group showed more microfracture changes in trabecular bone with more destructions of the tree-like mesh. Moreover, the collagen fibers were random rough with a fewer amount of bone lacunae in subchondral cortical plate in the osteoporotic OA group compared to the OA group. These findings indicated that the subchondral bone ultrastructure in the osteoporotic OA model was characterized by the destruction of the network structure and collagen fibers. The subchondral bone ultrastructural damage caused by osteoporosis may change mechanical properties of the upper cartilage and aggravate OA cartilage. Therefore, early diagnosis and treatment of osteoporosis is of great significance to prevent early OA from further developing osteoporotic OA.     

Aging and osteoarthritis: Central role of the extracellular matrix

Osteoarthritis (OA), is a major cause of severe joint pain, physical disability and quality of life impairment in the aging population across the developed and developing world. Increased catabolism in the extracellular matrix (ECM) of the articular cartilage is a key factor in the development and progression of OA. The molecular mechanisms leading to an impaired matrix turnover have not been fully clarified, however cellular senescence, increased expression of inflammatory mediators as well as oxidative stress in association with an inherently limited regenerative potential of the tissue, are all important contributors to OA development. All these factors are linked to and tend to be maximized by aging. Nonetheless the role of aging in compromising joint stability and function in OA has not been completely clarified yet. This review will systematically analyze cellular and structural changes taking place in the articular cartilage and bone in the pathogenesis of OA which are linked to aging. A particular emphasis will be placed on age-related changes in the phenotype of the articular chondrocytes.     

Growth‐related structural,biochemical, and mechanical properties of the functional bone–cartilage unit

Articular cartilage and subchondral bone act together, forming a unit as a weight‐bearing loading‐transmitting surface. A close interaction between both structures has been implicated during joint cartilage degeneration, but their coupling during normal growth and development is insufficiently understood. The purpose of the present study was to examine growth‐related changes of cartilage mechanical properties and to relate these changes to alterations in cartilage biochemical composition and subchondral bone structure. Tibiae and femora of both hindlimbs from 7‐ and 13‐week‐old (each n = 12) female Sprague‐Dawley rats were harvested. Samples were processed for structural, biochemical and mechanical analyses. Immunohistochemical staining and protein expression analyses of collagen II, collagen IX, COMP and matrilin‐3, histomorphometry of cartilage thickness and COMP staining height were performed. Furthermore, mechanical testing of articular cartilage and micro‐CT analysis of subchondral bone was conducted. Growth decreased cartilage thickness, paralleled by a functional condensation of the underlying subchondral bone due to enchondral ossification. Cartilage mechanical properties seem to be rather influenced by growth‐related changes in the assembly of major ECM proteins such as collagen II, collagen IX and matrilin‐3 than by growth‐related alterations in its underlying subchondral bone structure. Importantly, the present study provides a first insight into the growth‐related structural, biochemical and mechanical interaction of articular cartilage and subchondral bone. Finally, these data contribute to the general knowledge about the cooperation between the articular cartilage and subchondral bone.     

Parametric analysis of the stress distribution on the articular cartilage and subchondral bone

Few studies have stressed on the sensitivity of stress distribution in different mechanical properties of the articular cartilage and subchondral bone. The purpose of this study was to establish parametric variations of mechanical factors individually and examine how these biomechanical effects influenced the cartilage and subchondral bone plate stress fields in the hip joint. A finite element model including acetabulum and proximal femur was established to study the stress change associated with the thinning of cartilage, the increasing of subchondral bone modulus and the thickening of subchondral bone plate individually. The stress distributions in bone/cartilage interface were evaluated. Sensitivity of the stress magnitudes to the parametric changes was also analyzed. The results indicated that cartilage thinning has more significant effect than subchondral bone modulus increasing or thickening on the shear stress levels in subchondral bone/cartilage interface. Subchondral bone plate modulus increasing has mild effect on the shear stress in subchondral bone/cartilage interface. Cartilage thinning acts as a major influence on the development of the articular cartilage damage.     

Contrast-enhanced micro-computed tomography of compartment and time-dependent changes in femoral cartilage and subchondral plate in a murine model of osteoarthritis

A lack of understanding of the mechanisms underlying osteoarthritis (OA) progression limits the development of effective long-term treatments. Quantitatively tracking spatiotemporal patterns of cartilage and bone degeneration is critical for assessment of more appropriately targeted OA therapies. In this study, we use contrast-enhanced micro-computed tomography (μCT) to establish a timeline of subchondral plate (SCP) and cartilage changes in the murine femur after destabilization of the medial meniscus (DMM). We performed DMM or sham surgery in 10–12-week-old male C57Bl/6J mice. Femora were imaged using μCT after 0, 2, 4, or 8 weeks. Cartilage-optimized scans were performed after immersion in contrast agent CA4+. Bone mineral density distribution (BMDD), cartilage attenuation, SCP, and cartilage thickness and volume were measured, including lateral and medial femoral condyle and patellar groove compartments. As early as 2 weeks post-DMM, cartilage thickness significantly increased and cartilage attenuation, SCP volume, and BMDD mean significantly decreased. Trends in cartilage and SCP metrics within each joint compartment reflected those seen in global measurements, and both BMDD and SCP thickness were consistently greater in the lateral and medial condyles than the patellar groove. Sham surgery also resulted in significant changes to SCP and cartilage metrics, highlighting a potential limitation of using surgical models to study tissue morphology or composition changes during OA progression. Contrast-enhanced μCT analysis is an effective tool to monitor changes in morphology and composition of cartilage, and when combined with bone-optimized μCT, can be used to assess the progression of degenerative changes after joint injury.     

Selective estrogen receptor modulators (SERMs): New alternatives for osteoarthritis?

The dramatic rise in the prevalence rate of osteoarthritis (OA) after the menopause and the presence of estrogen receptors in joint tissues suggest that estrogen may help protect against the development of OA. Trials of estrogen therapy have produced inconclusive results, however, partly because of flaws in study design and partly because of the complexity of the mechanisms underlying estrogen's effects on joint tissues. Initial studies of the use of selective estrogen receptor modulators (SERMs) have reported beneficial effects in OA. These agents may exert both a direct effect upon joint cartilage and indirect effects on subchondral bone, synovium, muscle, tendons and ligaments. SERMs may be particularly beneficial for postmenopausal patients with osteoporotic OA, a phenotype defined by decreased bone density, associated with high remodeling in subchondral bone. More research is needed, though, before SERMs can become a therapeutic option for OA.