Racemization of aspartic acid in human articular cartilage.

The rate of racemization of aspartic acid was measured in young and aged human femoral head cartilage. Normal femoral heads were obtained at postmortem, osteoarthritic specimens at operations for total hip replacement. In order to distinguish between the aspartic acid racemization in collagen from that in proteoglycan (PG), in addition to native tissue, we tested cartilage specimens from which PG had been enzymatically removed. Preliminary results indicate that there is only a very slow collagen turnover in normal adult cartilage. The same is true of residual cartilage from osteoarthritic femoral heads, indicating no rapid repair except where osteophytes are formed. Native, PG-containing cartilage, whether normal or osteoarthritic was found to have unexpectedly high racemization rates.     

髋关节冠状断层影像解剖学

目的：为髋关节疾患的影像学诊断提供冠状断层解剖学基础。方法：成年男性右髋部标本5例(新鲜3，常规固定2)．先以解剖骨性标志画线．1例先作髋部冠状位MR1扫描．所有标本冻硬后．切制髋部冠状断层标本．结果：观察每一断层标小髓关节的主要结构、殴骨头韧带，髂股韧带和其周围组织的形态．位置、毗邻的特征及在连续断层的变化规伴；测量结果如下：股骨头垂直径41．2mm，冠状径42．9mm．髋臼冠状径52．7mm．髋臼深度29．6mm．股骨头及髋臼节软骨厚各为3.3mm与2．5mm，股骨头韧带长25．1mm，厚2．6mm．髂股韧带厚7．7mm。结论：髋关节的冠状断层解剖各结构形态、位置及变化规律．为临床骨科、影像学及髋关节镜技术诊断与治疗髋关节疾患，提供了有价值的形态学依据。     

CD44 expression is up-regulated in the deep zone of osteoarthritic cartilage from human femoral heads

 

Aims:

The objective of this study was to detail the topographical and zonal distribution of the cell adhesion molecule CD44 in normal and osteoarthritic cartilage.  

Methods and results:

Immunohistochemistry utilizing well characterized anti-CD44 antibodies (clones A3D8, Bric 235, 2C5) was performed on cryostat and paraffin sections of human articular cartilage from macroscopically normal ( n  = 18) and osteoarthritic ( n  = 11) femoral heads. Samples for cryostat sections were obtained from 12 topographically different sites. Sections were divided into zones (superficial, middle, deep) and the CD44 staining scored. Chondrocytes in normal articular cartilage and cartilage from osteoarthritic femoral heads stained positive for CD44 in both cryostat and paraffin sections. Normal cartilage showed a significant decrease in CD44 staining in the deep zone as compared to the superficial zone ( P  < 0.05). However, cryostat sections of residual cartilage from osteoarthritic femoral heads showed increased CD44 staining in the deep zone as compared to normal articular cartilage. The CD44 staining showed no topographical variation in either the normal cartilage or the osteoarthritic residual cartilage.  

Conclusions:

CD44 expression displays a distinct zonal variation in normal articular cartilage which is lost in osteoarthritic cartilage due to an up-regulated expression in the deep zone. CD44 expression does not exhibit topographical variation.     

Assessing macroscopic and microscopic indicators of osteoarthritis in the distal interphalangeal joints: a cadaveric study

Osteoarthritis is manifested both by macroscopically visible lesions and by specific histological indicators. Although traditional views of the disease process invoke physical abrasion of joint surfaces, recent studies indicate that tissue-level changes may precede grossly visible lesions of articular cartilage. This study investigates the association between gross and histological indicators of osteoarthritis at the manual interphalangeal joints, and examines a sequence of events that may lead to the onset of cartilage degeneration. Interphalangeal joints from the hands of nine cadavers were dissected, of which 52 joints were collected and further evaluated. Gross degradation of the proximal articular surface was graded on a scale of 0-3 (with 0 representing normal cartilage with no visible lesions). Osteoarthritic lesions were found in 86% of specimens and showed no preferential occurrence between males and females or right and left hands. Histological analysis indicated that known microscopic indicators of osteoarthritis always occur in Grade 1-3 specimens, but can also be recognized in some macroscopically normal specimens. Many macroscopically normal specimens exhibited chondrocyte clustering (28.6%) and/or tide mark irregularities (57%), indicating that these features are most likely the earliest to develop in the progression of osteoarthritis. It is possible that the initiating etiology is thickening of the subchondral bone, but this was not directly observed. Results indicate significant thinning of the cartilage as macroscopic degradation progresses. Our study supports, with slight modification, a previously proposed cascade of histological changes that may ultimately lead to the physical destruction of articular cartilage.     

Evaluation of correlation of articular cartilage staining for DDR2 and proteoglycans with histological tissue damage and the results of radiographic assessment in patients with early stages of knee osteoarthritis

Objective: To determine, if staining of articular cartilage for proteoglycans (natural element of healthy and functioning cartilage) and discoidin domain receptor 2 (DDR2) (a protein associated with articular cartilage degradation) is correlated with histological tissue damage or radiographic assessment score in patients with early stages of knee osteoarthritis (OA). Method: 40 patients, with early stage OA were enrolled, from whom the biopsies for histological and immunohistochemical studies were obtained from edge of the femoral condyle during the arthroscopy. Semi-quantitative computer based analysis was used to evaluate the proportion of staining in histological sections. Results: No correlation was shown between the proportion of tissue stained for DDR2 and histological score or the results of radiographic assessment of tibiofemoral (TF) joint. There was a negative correlation between the proportion of tissue stained for DDR2 and radiographic grade of patellofemoral (PF) OA (Spearman r=-0.34; 95% CI -0.60 to -0.02; P=0.03). No correlation was shown between the proportion of tissue stained for proteoglycans and histological score or the results of radiographic assessment of TF and PF joints. A negative correlation was found between proportion of tissue stained for DDR2 and proteoglycans. Spearman r=-0.43; 95% CI=-0.66 to -0.12; P=0.006. Conclusion: Production of DDR2 in articular cartilage could be related to early stages of OA, as it is significantly correlated to decrease of staining for cartilage proteoglycans. The role of production of DDR2 in cartilage may be decreased in stages, where higher grades of OA are detected on the radiographs.     

Cleavage of type II collagen by cathepsin K in human osteoarthritic cartilage

Cathepsin K is a cysteine protease of the papain family that cleaves triple-helical type II collagen, the major structural component of the extracellular matrix of articular cartilage. In osteoarthritis (OA), the anabolic/catabolic balance of articular cartilage is disrupted with the excessive cleavage of collagen II by collagenases or matrix metalloproteinases. A polyclonal antibody against a C-terminal neoepitope (C2K) generated in triple-helical type II collagen by the proteolytic action of cathepsin K was prepared and used to develop an enzyme-linked immunosorbent assay to study the generation of this epitope and the effects of its presence in normal adult and osteoarthritic femoral condylar articular cartilage. The generation of the C2K epitope in explant culture and the effect of a specific cathepsin K inhibitor were studied. The neoepitope, which is not generated by the collagenase matrix metalloproteinase-13, increased with age in articular cartilage and was significantly elevated in osteoarthritic cartilage compared with adult nonarthritic cartilage. Moreover, in explants from three of eight OA patients, the generation of the neoepitope in culture was significantly reduced by a specific, nontoxic inhibitor of cathepsin K. These data suggest that cathepsin K is involved in the cleavage of type II collagen in human articular cartilage in certain OA patients and that it may play a role in both OA pathophysiology and the aging process.     

Microscopic Change in Macroscopically Normal Equine Cartilage from Osteoarthritic Joints

The objective of this study was to assess whether macroscopically normal articular cartilage taken from joints containing focal osteoarthritic lesions is histologically similar to articular cartilage taken from macroscopically normal joints. Metacarpophalangeal, proximal interphalangeal, and distal interphalangeal joints were obtained from 10 horses following euthanasia. Gross articular cartilage damage was scored and the cartilage assigned to one of two groups: (1) macroscopically normal cartilage from normal joints (control) and (2) macroscopically normal cartilage from diseased joints in which there were focal osteoarthritic lesions. Chondrocytes expressing specific cytokines and cytokine receptors were identified by immunohistochemistry. The total number of chondrocytes, and percentage of chondrocytes positive for these cytokines and receptors, was recorded in the superficial, middle, and deep cartilage zones. There was a significant increase in the expression of interleukin-1β in the superficial and middle zones and interleukin-18 receptor in the superficial zone in Group 2 compared with Group 1 control samples. A significant positive correlation also was found between the grade of osteoarthritis and the percentage of chondrocytes positive for interleukin-1β in the superficial and middle zones, and for interleukin-18 and interleukin-18R in the superficial zone. There was a significant increase in histology score for glycosaminoglycan loss in Group 2 compared with that in Group 1. In joints with focal osteoarthritis lesions, all the articular cartilage, even if macroscopically apparently normal, may have microscopic changes associated with osteoarthritis.     

Articular cartilage defects: study of 25,124 knee arthroscopies

This retrospective study aimed to provide data on the prevalence, epidemiology and etiology of the knee articular cartilage lesions and describe and estimate, on the ground of a large database, the number of patients who might benefit from cartilage repair surgery. The analysis of 25,124 knee arthroscopies performed from 1989 to 2004 was conducted. Information concerning cartilage lesion, associated articular lesions and performed procedure were collected. Cartilage lesions were classified in accordance with the Outerbridge classification. Chondral lesions were found in 60% of the patients. Documented cartilage lesions were classified as localized focal osteochondral or chondral lesion in 67%, osteoarthritis in 29%, osteochondritis dissecans in 2% and other types in 1%. Non-isolated cartilage lesions accounted for 70% and isolated lesions accounted for 30%. The patellar articular surface (36%) and the medial femoral condyle (34%) were the most frequent localization of the cartilage lesions. Grade II according to Outerbridge classification was the most frequent grade of the cartilage lesion (42%). The most common associated articular lesions were the medial meniscus tear (37%) and the injury of the anterior crucial ligament (36%). Articular cartilage lesions are a common pathology of the knee joint. The potential candidates for cartilage repair surgery, patients with one to three localized grade III and IV cartilage lesions, under the age of 40 were found in 7% and under the age of 50 years in 9% of all analysed patients. However, because these patients are a heterogeneous group and the natural history of cartilage lesions remains so far unknown, also the total number of patients in our study, who might benefit from cartilage repair, remains unknown precisely.     

Microscopic change in macroscopically normal equine cartilage from osteoarthritic joints

The objective of this study was to assess whether macroscopically normal articular cartilage taken from joints containing focal osteoarthritic lesions is histologically similar to articular cartilage taken from macroscopically normal joints. Metacarpophalangeal, proximal interphalangeal, and distal interphalangeal joints were obtained from 10 horses following euthanasia. Gross articular cartilage damage was scored and the cartilage assigned to one of two groups: (1) macroscopically normal cartilage from normal joints (control) and (2) macroscopically normal cartilage from diseased joints in which there were focal osteoarthritic lesions. Chondrocytes expressing specific cytokines and cytokine receptors were identified by immunohistochemistry. The total number of chondrocytes, and percentage of chondrocytes positive for these cytokines and receptors, was recorded in the superficial, middle, and deep cartilage zones. There was a significant increase in the expression of interleukin-1beta in the superficial and middle zones and interleukin-18 receptor in the superficial zone in Group 2 compared with Group 1 control samples. A significant positive correlation also was found between the grade of osteoarthritis and the percentage of chondrocytes positive for interleukin-1beta in the superficial and middle zones, and for interleukin-18 and interleukin-18R in the superficial zone. There was a significant increase in histology score for glycosaminoglycan loss in Group 2 compared with that in Group 1. In joints with focal osteoarthritis lesions, all the articular cartilage, even if macroscopically apparently normal, may have microscopic changes associated with osteoarthritis.     

Bilateral coxofemoral degenerative joint disease in a juvenile male yellow-eyed penguin (Megadyptes antipodes)

A juvenile, male, yellow-eyed penguin (Megadyptes antipodes) with abnormal stance and decreased mobility was captured, held in captivity for approximately 6 weeks, and euthanized due to continued clinical signs. Radiographically, there was bilateral degenerative joint disease with coxofemoral periarticular osteophyte formation. Grossly, the bird had bilaterally distended, thickened coxofemoral joints with increased laxity, and small, roughened and angular femoral heads. Histologically, the left femoral articular cartilage and subchondral bone were absent, and the remaining femoral head consisted of trabecular bone overlain by fibrin and granulation tissue. There was no gross or histological evidence of infection. The historic, gross, radiographic, and histopathologic findings were most consistent with bilateral aseptic femoral head degeneration resulting in degenerative joint disease. Although the chronicity of the lesions masked the initiating cause, the probable underlying causes of aseptic bilateral femoral head degeneration in a young animal are osteonecrosis and osteochondrosis of the femoral head. To our knowledge, this is the first reported case of bilateral coxofemoral degenerative joint disease in a penguin.     

The relationship between ultra-short telomeres,aging of articular cartilage and the development of human hip osteoarthritis

Introduction

Ultra-short telomeres caused by stress-induced telomere shortening are suggested to induce chondrocyte senescence in human osteoarthritic knees. Here we have further investigated the role of ultra-short telomeres in the development of osteoarthritis (OA) and in aging of articular cartilage in human hips.

Materials and methods

Cartilage was obtained from four different distances of the central weight-bearing area in human femoral heads (14 OA and 9 non-OA). Samples were split into three: one for quantification of ultra-short single telomeres by Universal STELA and mean telomere length measurement by Q-PCR; one for histological grading of OA, and one for immunohistochemical staining.

Results

Load of ultra-short telomeres increased closer to the central weight-bearing area and correlated with cartilage degradation in both OA and non-OA samples. Mean telomere length decreased with decreasing distance to the central weight-bearing area, however, unexpectedly increased in the most central zone. This increase was associated with immunohistochemical findings of cells expressing markers characteristic of progenitor-like cells.

Conclusion

These findings suggest a role of short telomeres in the development of OA and in aging of articular cartilage. Furthermore, progenitor-like cells with long telomeres may be recruited to the most damaged areas of the cartilage.     

冷冻保存异体骨膜移植治疗髋关节骨性关节炎

目的：报道采用冷冻保存胚胎颅骨骨膜移植修复髋关节软骨大面积缺损的治疗结果。方法：自1990年5月—1994年4月，对42例(47侧)髋关节软骨全厚缺损采用冷冻保存胚胎颅骨骨膜移植进行修复，其中14例股骨头骨质重度坏死者，同时施行带旋髂深血管髂骨植骨。对34例(38侧)髋关节进行了2～6年(平均40个月)随访。结果：按照吴之康髋关节人工置换术后疗效评定标准．术前平均得分6．4分，术后平均得分15.8分，优良25例，很好5例，好3例，尚可1例。结论：与自体移植物修复关节软骨大面积缺损相比，本方法无附加损伤，具有移植材料来源充分，取材量大．形态与股骨头相似等特点，是治疗髋关节软骨大面积缺损的一种有效方法。     

Anatomical study of the articular branches innervated the hip and knee joint with reference to mechanism of referral pain in hip joint disease patients

Introduction : Referred pain in the anterior knee joint is the most common symptom in hip disease patients. The development of referred pain is considered to be related to dichotomizing peripheral sensory fibers. However, no gross anatomical findings identify any dichotomizing fibers innervating both the hip and knee joints. We dissected the femoral and obturator nerves in human cadavers to investigate the distribution of the articular branches in the hip and knee joints. Fourteen embalmed left lower limbs from 14 Japanese adult cadavers (five from females, nine from males, average age 73.8 ± 14.1 years) were observed macroscopically. The articular branches of the femoral and obturator nerves were dissected at the anterior margin of the groin toward the thigh region. After dissections of the articular nerves of the hip joints, the femoral and obturator nerves were exposed from proximally to distally to identify the articular nerves of the knee joints. The branching pattern of the articular branches in the hip and knee joints was recorded. In six of 14 limbs (42.9%), the femoral nerve supplied articular branches to the anteromedial aspect of both the hip and knee joints. These articular branches were derived from the same bundle of femoral nerve. These gross anatomical findings suggested that dichotomizing peripheral sensory fibers innervate the hip and knee joints and these could relate to the referred pain confirmed in the anterior knee joints of patients with hip disease. Clin. Anat. 31:705–709, 2018. © 2018 Wiley Periodicals, Inc.     

The effects of hip contact aberrations on stress patterns within the human femoral head

A two-dimensional finite element model incorporating cancellous bone inhomogeneity is used to study femoral head stress alterations caused by changes from the usual articular contact patterns. The contact stress distributions, calculated from an earlier mathematical analysis by Greenwald and O'Connor (16), are found to influence not only the adjacent subchondral bone, but relatively distant parts of the head as well. Both abnormally large joint incongruity and abnormally low cartilage compliance cause load to shift away from the superior “weight-bearing” area, out toward the periphery of the contact region. As a consequence, transverse compressive stresses, which are of appreciable magnitude but which do not contribute to weight bearing, are built up throughout much of the superior and central portions of the femoral head. Most small changes in the overall cartilage thickness or in its thickness distribution, when considered in isolation from hip compliance changes, have only minor effects on the internal stress distribution. An important exception is cartilage thinning at the superior margin, which can result in abrupt longitudinal compressive stress concentrations. It is suggested that such alterations of the normal patterns of stress transmission may contribute to sclerosis or to the formation of osteophytes or cysts in the osteoarthritic hip. This study was aided by grants from the Easter Seal Research Foundation (#N7739), the National Science Foundation (#ENG78-05451), the Barra Foundation, Inc., and the Western Pennsylvania Chapter of the Arthritis Foundation. The authors wish to acknowledge the excellent service provided by the University of Pittsburgh Computer Center. The assistance of Mr. Gary E. Graf and Mrs. Diana W. Montgomery are also appreciated.     

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。     

Nanomechanical properties and mineral concentration in articular calcified cartilage and subchondral bone

We studied articular calcified cartilage (ACC) and the immediately subchondral bone (SCB) in normal and osteoarthritic human femoral heads. Thick slices of human normal reference post mortem (PM) and osteoarthritic (OA) femoral heads (age 55-89 years) were embedded in PMMA, micromilled, carbon coated and studied using quantitative backscattered electron (qBSE) imaging to determine variations in degree of mineralization. With exact microanatomical location, nanoindentation was performed on the same block faces in representative superior (more highly loaded) and medial regions of the joint surface. Using a partial unloading method, elastic modulus as a function of indenter penetration depth was determined using a spherical tipped diamond indenter. A pointed indenter was used to determine the tissue hardness in selected locations. The relationship between mineralization and indentation modulus was more distinct in ACC than in SCB, the latter having a higher matrix concentration with variable collagen orientation. In OA, the bulk of the measurements were coincident with those in the PM samples, although there was a greater range in the levels of mineralization and modulus in ACC. In OA, extremely hypermineralized ACC was found in ACC proper, especially in superior regions, and translocated into SCB and hyaline cartilage. The very highly mineralized cartilage fragments may function as a hard grinding abrasive, accelerating wear rates whether attached to or fragmented from the eburnated surfaces of OA ACC. Highly mineralized regions would also alter loading patterns and thereby contribute to further destruction of the joint tissues.     

Localization of matrix metalloproteinase 3 (stromelysin) in osteoarthritic cartilage and synovium.

Degradation of proteoglycans is an initial change in osteoarthritic cartilage. Matrix metalloproteinase-3 (MMP-3; stromelysin) capable of degrading cartilage proteoglycans and type IX collagen was immunolocalized in osteoarthritic and normal cartilage. Immunohistochemical studies showed MMP-3 in chondrocytes of the superficial and transition zones in approximately 90% of osteoarthritic cartilage (60 of 67 samples) and in 31% of those of the superficial zone in some normal cartilage (4 of 13 samples). MMP-3 staining correlated directly with the histological histochemical scores of Mankin and with proteoglycan depletion, up to a certain grade of severity. Chondrocytes in the deep radial zone, clusters, and osteophytes were immunostained only when proteoglycan depletion and fissures affected them. Culture media from osteoarthritic cartilage contained significantly higher levels of metalloproteinase activity that was identified as MMP-3 by immunoblotting and lower amounts of tissue inhibitor of metalloproteinases compared with those in the control samples. MMP-3 was also immunolocalized in the lining cells of most osteoarthritic synovium (20 of 23 specimens, 87%) with a direct correlation with scores of inflammatory cell infiltration in the synovium, but it was not detected in the normal synovium. Light and electron microscopic studies demonstrated that MMP-3 digests proteoglycan aggregates in human articular cartilage. Treatment of normal and osteoarthritic cartilage slices with tumor necrosis factor-alpha and/or interleukin-1 alpha increased the number of MMP-3-immunoreactive chondrocytes and the intensity of the staining. These data suggest that MMP-3 produced by the chondrocytes and synovial lining cells under stimulation with these cytokines may be important in proteoglycan degradation in human ostoearthritic cartilage.     

Silicon Dioxide Particles Deposited in Vessels and Cartilage of the Femoral Head

Silicosis had been considered for decades as an illness with manifestations of lung fibrosis due to inhalation of overconcentrated SiO₂ dust. To the best of our knowledge, studies have yet to report SiO₂ deposits in any other tissues and organs. In the present case, while performing bilateral artificial total hip arthroplasty for one patient, we found that the articular cartilage of the bilateral femoral head was black. Therefore, specimens thereof were sent for pathological examination. Pathological examination (immunohistochemistry) and polarized light microscopy revealed the presence of considerable brown, acicular, rhombic, and crumb-like crystals. The crystals were mainly composed of SiO₂. SiO₂ could deposit in vessels and femoral head cartilage via blood circulation.     

Contiguous development of idiopathic osteonecrosis and osteoarthrosis in ischemia of a femoral head (radiological and morphological study)

In a 67 year-old man, an aseptic necrosis of the right hip joint developed side by side with an early oteoarthrosis characterized by an extensive narrowing of the upper interlinear space. The histological study revealed a diffuse ischemia which had evolved differently in the various regions of the femoral head. A well-limited necrosis appeared in a part of the weight-bearing zone, and osteoarthrosis developed in another one. In contrast with classical osteoarthrosis secondary to malformation, the osteoarthrotic lesions of the weight-bearing zone were caused by the ischemic angio-fibrosis of the bone marrow. At the beginning there was a resorption by the subjacent fibro-vascular tissue of the end-plate and of the deep layer of the cartilage. The osteosclerosis of this zone, in particular the eburnated plate, was formed mostly of fibre bone which rapidly became necrotic. Outside the weight-bearing zone, the subchondral angio-fibrosis and the non-inflammatory vascular pannus modified the articular surface.     

Cell–tissue interactions in osteoarthritic human hip joint articular cartilage

Volume and morphology of chondrocytes in osteoarthritic human hip joint articular cartilage were characterized, and their relationship to tissue structure and function was determined. Human osteochondral articular cartilage samples (n?=?16) were obtained from the femoral heads of nine patients undergoing total hip arthroplasty due to osteoarthritis (OA). Superficial chondrocytes (N?=?65) were imaged in situ with a confocal laser scanning microscope at 37?°C. This was followed by the determination of the mechanical properties of the tissue samples, depth-wise characterization of cell morphology (height, width; N?=?385) as well as structure and composition of the tissues using light microscopy, digital densitometry, Fourier transform infrared microspectroscopy and polarized light microscopy. Significant correlations were found between the cell volume and the orientation angle associated with the collagen fibers (r?=?0.320, p?=?0.009) as well as between the cell volume and the initial dynamic modulus of the tissue (r?=??0.305, p?=?0.013). Furthermore, the depth-dependent chondrocyte aspect ratio (height/width) correlated significantly with the orientation angle of the collagen fibers and with the tissue’s proteoglycan content (r?=?0.261 and r?=?0.228, respectively, p?相似文献