Klaus E. Kuettner's research while affiliated with Rush Medical College and other places
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Publications (246)
Successful and cartilage-specific cultivation of chondrocytes requires a stable phenotype during the in vitro culture period. This is based on a differentiated extracellular matrix synthesis. The alginate system as a three-dimensional support is a useful system to culture chondrocytes and to analyze the biochemical processes in this system. Talar c...
Objective:
Superficial articular chondrocytes display distinct spatial remodeling processes in response to the onset of distant osteoarthritis (OA). Such processes may be used to diagnose early events before manifest OA results in tissue destruction and clinical symptoms. Using a novel method of spatial quantification by calculating the angles bet...
Objective:
The zonal composition and functioning of adult articular cartilage causes depth-dependent responses to compressive injury. In immature cartilage, shear and compressive moduli as well as collagen and sulfated glycosaminoglycan (sGAG) content also vary with depth. However, there is little understanding of the depth-dependent damage caused...
Human superficial chondrocytes show distinct spatial organizations, and they commonly aggregate near osteoarthritic (OA) fissures. The aim of this study was to determine whether remodeling or destruction of the spatial chondrocyte organization might occur at a distance from focal (early) lesions in patients with OA.
Samples of intact cartilage (con...
Periprosthetic osteolysis with or without aseptic loosening is a major clinical problem in total hip arthroplasty. While the macrophage response to prosthetic wear debris and its role in periprosthetic osteolysis has been extensively studied, information regarding other cell types (fibroblasts, osteoblasts) is limited. This study explored the respo...
A better understanding of the unique cellular and functional properties of the superficial zone of articular cartilage may aid current strategies in tissue engineering which attempts a layered design for the repair of cartilage lesions to avert or postpone the onset of osteoarthritis. However, data pertaining to the cellular organization of non-deg...
While traumatic joint injuries are known to increase the risk of osteoarthritis (OA), the mechanism is not known. Models for injurious compression of cartilage may identify predictors of injury that suggest a clinical mechanism. We investigated the relationship between peak stress during compression and glycosaminoglycan (GAG) loss after injury for...
The incidence of degenerative changes and osteoarthritis is lower in the ankle than in the knee joints. This cannot be explained exclusively with differences in anatomy and biomechanical properties of these two synovial joints. Previous studies have indicated distinct differences in the biochemical composition of the extracellular matrix of articul...
Background
The incidence of degenerative changes and osteoarthritis is lower in the ankle than in the knee joints. This cannot be explained exclusively with differences in anatomy and biomechanical properties of these two synovial joints. Previous studies have indicated distinct differences in the biochemical composition of the extracellular matrix...
Although cartilage lesions occur in the ankles, osteoarthritis rarely develops in the ankles, suggesting that ankle cartilage can up-regulate mechanisms to repair the damaged matrix. To define these processes, we compared cartilage samples obtained from normal tali and from lesional sites of damaged tali.
Cartilage samples were obtained from the ta...
The loss of tissue thickness and associated changes in Diffraction-enhanced X-ray (DEI) images, as well as changes in histological and DEI much more so 80% injury were consistent with irreversible tissue compaction and structural damage to cartilage and its collagen network. These changes were more profound for immature bovine compared to the adult...
The assessment of articular cartilage integrity is of value for the detection of early degenerative joint disease in both the clinical and the research settings. It was the purpose of this study to determine the accuracy and reliability of identifying articular cartilage defects through Diffraction Enhanced Imaging (DEI), a high contrast radiograph...
Variations among joints in the initiation and progression of degeneration may be explained, in part, by metabolic, biochemical and biomechanical differences. Compared to the cartilage in the knee joint, ankle cartilage has a higher content of proteoglycans and water, as well as an increased rate of proteoglycan turnover and synthesis, all of which...
To delineate the role of endogenous osteogenic protein 1 (OP-1) in human articular cartilage homeostasis via the inhibition of OP-1 gene expression by antisense oligonucleotides.
Human adult normal articular cartilage was obtained from the knee and ankle joints of 34 organ donors. Chondrocytes were cultured as tissue explants or isolated cells in a...
To determine whether there are differences in matrix turnover within early cartilage lesions of the ankle (talocrural) joint compared with the knee (tibiofemoral) joint that may help explain differences in the prevalence of osteoarthritis in these 2 joints.
Cartilage removed from lesions of the tali and femoral condyles was analyzed for type IIB co...
Our data suggest that macroscopically intact looking talus dome cartilage of degenerative human ankle joints (non-adjacent to the OA-lesion) showed an increased equilibrium stiffness of its deeper zones and an unchanged superficial stiffness. Injurious compression of this tissue and of normal talus cartilage showed neither tissue compaction nor cha...
PURPOSE
The goal of this work is to determine the effecacy of Diffraction Enhanced Radiographic Imaging (DEI) for the identification of tendon lesions. Because the details of soft tissue are not visible with conventional radiography, DEI, which enables the visualization of articular cartilage, tendons, and ligaments, is evaluated here for detection...
Non-calcified tissues, including tendons, ligaments, adipose tissue and cartilage, are not visible, for any practical purposes, with conventional X-ray imaging. Therefore, any pathological changes in these tissues generally necessitate detection through magnetic resonance imaging or ultrasound technology. Until recently the development of an X-ray...
To determine the feasibility of detecting the structural orientation in cartilage with Diffraction Enhanced X-Ray Imaging.
Human tali and femoral head specimens were Diffraction Enhanced X-Ray Imaged (DEI) at the SYRMEP beamline at Elettra at various energy levels to detect the architectural arrangement of collagen within cartilage. DEI utilizes a...
Der humane hyaline Knorpel ist ein hypozelluläres, avaskuläres, aneurales und alymphatisches Gewebe, das die artikulierenden Knochenenden eines synovialen Gelenkes überzieht. Es besteht aus Chondrozyten und einer extrazellulären Matrix, welche hauptsächlich aus Kollagenen und Proteoglykanen besteht. Das Verhältnis der Matrixkomponenten zueinander b...
In the normal femur, tibia and talus the superficial zone contained significantly more cells than did the deeper zones. With early degenerative changes the cell density of the deeper zones did not change. However, except for the tibia, there were changes in the superficial zones with degeneration. The cell density of both the talus and femur increa...
Our data suggest that human degenerative cartilages from talus and femoral cartilage exhibit significant differences between superficial and deeper zones in their mechanical properties and their response to our choice of injurious compression. Injurious compression did not affect the equilibrium modulus of degenerative talus cartilage; however, inj...
Destruction and loss of articular cartilage is one of the key events in osteoarthritic disorders. Radiographic evaluation is based solely on detecting the narrowing of the joint space and not on destruction of cartilage, since cartilage tissue is invisible in conventional X-ray imaging. Here we report that a high resolution image of human articular...
A synchronized balance between synthesis and breakdown of extracellular matrix (ECM) molecules in normal articular cartilage is disturbed in osteoarthritis (OA). The focus of our study is the anabolic factor, osteogenic protein-1 (OP-1) that is expressed in articular cartilage and is able to induce the synthesis of ECM components. The major aim was...
The purpose of this review is to summarize the current scientific knowledge of bone morphogenetic proteins (BMPs) in adult articular cartilage. We specifically focus on adult cartilage, since one of the major potential applications of the members of the BMP family may be a repair of adult tissue after trauma and/or disease. After reviewing cartilag...
Osteogenic protein-1 (OP-1, BMP-7) induces bone formation and cartilage growth. Since OP-1 is an anabolic factor expressed by human articular chondrocytes, we examined the response of endogenous OP-1 to interleukin-1beta (IL-1beta) in human articular cartilage.
Normal adult human articular cartilage explants were cultured for twenty-five days in th...
Degenerative changes in the tall and femoral distal cartilages of more than 2,000 tissue donors were graded based on the appearance of articular cartilage and osteophytes. In the ankle and the knee the degenerative changes increased with age; however, the rate of degeneration in the ankle was slower than in the knee. The degenerative changes in the...
Non-calcified tissues, including tendons, ligaments, adipose tissue and cartilage, are not visible, for any practical purposes, with conventional X-ray imaging. Therefore, any pathological changes in these tissues generally necessitate detection through magnetic resonance imaging or ultrasound technology. Until recently the development of an X-ray...
Articular cartilage of synovial joints is not visible with conventional X-ray imaging. Hence, the gradual degeneration and destruction of articular cartilage, which is characteristic of degenerative joint diseases, is only detected at a late stage when the cartilage is lost and the joint space that it once occupied narrows. The development of an X-...
Non-calcified tissues, including tendons, ligaments, adipose tissue and cartilage, are not visible, for any practical purposes, with conventional X-ray imaging. Therefore, any pathological changes in these tissues generally necessitate detection through magnetic resonance imaging or ultrasound technology. Until recently the development of an X-ray...
Tissue engineering als ein interdisziplinäres Forschungsgebiet wird heutzutage als Brücke zwischen der Entwicklung und dem Verständnis von Zellmechanismen sowie der Überleitung zu biologischen und klinischen Anwendungen verstanden. Ziel sollte die Herstellung, Erhaltung oder Weiterentwicklung eines Gewebes sein. Unterschiedliche Strategien zur Entw...
We assessed the distribution and relative immunohistochemical staining intensity of the bone morphogenetic protein-7, osteogenic protein-1 (OP-1), in its pro- and mature forms, and four of its receptors, type I (ALK-2, ALK-3, and ALK-6) and type II in normal adolescent New Zealand White rabbit articular cartilage. Expression of the protein and its...
Articular cartilage has a poor reparative capacity. This feature is exacerbated with aging and during degenerative joint conditions, contributing to loss of motion and impairment of quality of life. This study focused on osteogenic protein-1 (OP-1) and its ability to serve as a repair-stimulating factor in articular cartilage. The purpose of this w...
To study age-related (as opposed to arthritis-related) changes in collagen and proteoglycan turnover.
Macroscopically nondegenerate normal ankle cartilage obtained from 30 donors (ages 16-75 years) was processed for in situ hybridization to detect messenger RNA (mRNA) of type IIB collagen (CIIB); antibodies to the C-propeptide of type II collagen (...
The prevalence of osteoarthritis (OA) is lower in some joints, i.e., the ankle, than in the knee. We have compared the cartilages from these two joints of the same limb in adult donors (matched pairs). Our data to date suggest that there are metabolic, biochemical and biomechanical differences between the cartilages of the two joints. The current s...
Osteoarthritis is a progressive disease that is initiated at the surface of articular cartilage and proceeds to destroy the entire depth of the cartilage. The prevalence of osteoarthritis varies in different joints; e.g., the ankle joint has a very low prevalence of the disease compared to the knee joint. To better understand any inherent differenc...
To introduce a novel X-ray technology, diffraction-enhanced X-ray imaging (DEI), in its early stages of development, for the imaging of articular cartilage.
Disarticulated and/or intact human knee and talocrural joints displaying both undegenerated and degenerated articular cartilage were imaged with DEI. A series of three silicon crystals were use...
The purpose of this work was to test the effect of inhibition of bone remodeling, through the use of the bisphosphonate, zoledronic acid, on cartilage matrix damage in an animal model of cartilage matrix damage.
New Zealand white rabbits were divided into four groups for treatment purposes: (1) untreated controls; (2) injected into one knee joint w...
The unique biomechanical properties of healthy cartilage ensure that articular cartilage is able to transmit force between the joints while maintaining almost friction-free limb movement. In osteoarthritis, the biomechanical properties are compromised, but we still do not understood whether this precedes the onset of the disease or is a result of i...
The molecular program of a cell determines responses including induction or inhibition of genes for function and activity, and this is true of the cells within articular cartilage, a major functional component of the joint. While our studies have previously focussed on differences in the molecular programs of the cells within the superficial and de...
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...
Several studies have shown less prevalence of degenerative changes and osteoarthritis in ankle than in knee joints [1–3].This cannot be explained exclusively with differences in anatomy and biomechanical properties [4],especially since the ankle surface is exposed to higher loads per unit surface area than the knee. Rather, the contribution of stru...
Each joint surface has a unique, joint-specific superficial and deep cell density and a fixed ratio of those. In the lower extremity, the cell densities of both, superficial and deep layers, increase in the same order from talus dome, proximal tibia, distal tibia to distal femur, regardless of different age groups or Collins Grades of the talus dom...
Our studies of human articular cartilages began approximately 13 years ago when collaboration was established between the Department of Biochemistry of Rush Medical College and the Regional Organ Bank of Illinois. As of April 2001, this collaboration has resulted in the acquisition of cartilages from more than 1900 different donors, including about...
The detection of articular cartilage and its abnormalities through non-invasive means is of importance for the early diagnosis of the degenerative joint disease, osteoarthritis (OA). The development of treatment strategies depends largely on the ability to identify early pathological changes in the articular cartilage and monitor the progression of...
Clinical and epidemiological data provide evidence that the prevalence of symptomatic osteoarthritis (OA) is higher in knee than in ankle joints. Several factors can contribute to this phenomenon, including a difference in biochemical composition and gene expression levels. This difference in composition may provide the ankle tissue with more resis...
Cartilage regeneration and repair is one of the major obstacles to treat arthritic diseases. The members of the bone morphogenetic protein (BMP) family of the transforming growth factor-β (TGFβ) superfamily received a high degree of attention among factors potentially capable of inducing and promoting anabolic processes in articular cartilage [1, 2...
Superficial zone protein (SZP) is a 345 kDa glycoprotein which contains chondroitin sulfate and keratan sulfate chains [1]. The molecule is synthesized by the superficial zone chondrocytes of articular cartilage, but not by middle and deep zone chondrocytes. It is also made by synovial cells and is present in synovial fluid. SZP shows a high degree...
Osteoarthritis (OA) is characterized by the failure of anabolic processes to keep up with an acceleration in catabolic processes. The role that inflammation, trauma, instability and other factors play in the initiation and progression of OA are still poorly understood [1, 2]. A possible approach to slow down the degeneration of the articular surfac...
The human and the dog meniscal horns and the body consist of morphologically distinct cell classes that vary in shape and size. For the first time the present study identifies SZP expression in the human and the dog menisci and links this expression only to the meniscal body while the anterior and posterior meniscal horns are not involved. This ess...
Articular cartilage contains four distinct zones, extending from the surface to the subchondral bone. Freshly isolated chondrocytes from the superficial zone of articular cartilage retain a collagenase-P-resistant cell-associated matrix. In the studies described here, the protein Del1 was identified as a component of the cell-associated matrix of s...
In this report we describe the purification of human superficial zone protein (SZP), the generation of cross-species monoclonal antibodies (MAbs) and the detection of this protein in human and animal body fluids. Human SZPs, used as immunizing antigens, were purified either from culture media of human cartilage organ cultures or from human synovial...
Articular hyaline cartilage takes on the contours of the subchondral bone on which it lies, but its thickness varies between joints, within a single joint and within a single articular surface. Previous studies have correlated articular cartilage thickness distribution with the degree of stress and weight bearing on joint surfaces, but few studies...
Articular hyaline cartilage takes on the contours of the subchondral bone on which it lies, but its thickness varies between joints, within a single joint and within a single articular surface. Previous studies have correlated articular cartilage thickness distribution with the degree of stress and weight bearing on joint surfaces, but few studies...
Nonsteroidal antiinflammatory drugs(NSAIDs) are known as clinically effective agents for treatment of inflammatory diseases. Inhibition of cyclooxygenase has been thought to be a major facet of the pharmacological mechanism of NSAIDs. However, it is difficult to ascribe the antiinflammatory effects of NSAIDs solely to the inhibition of prostaglandi...
Cartilage was obtained from eight matched knee (tibiofemoral and femoropatellar) and ankle (talocrural) joints of five different donors (both left and right from donors 14, 22, and 38 years of age, and left only from donors 31 and 45 years of age) within 24 hours of death. All cartilage was graded as normal by the macroscopic visual Collins' scale...
Objective
To determine the role of CD44-mediated matrix assembly in maintaining cartilage homeostasis.Methods
Articular cartilage tissue slices as well as isolated chondrocytes were treated with hyaluronan (HA) hexasaccharides. Tissues and cells were processed for histology, immunohistochemistry, colorimetric assay, reverse transcriptase–polymerase...
We have used recombinant osteogenic protein-1 to investigate our hypothesis that proper repair and maintenance of cartilage requires not only enhanced biosynthesis and replenishment of the extracellular matrix but also the enhancement of components necessary for matrix retention.
The effects of osteogenic protein-1 were examined on bovine articular...
Successful and cartilage-specific cultivation of chondrocytes requires a stable phenotype during the in vitro culture period. This is based on a differentiated extracellular matrix synthesis. The alginate system as a three-dimensional support is a useful system to culture chondrocytes and to analyze the biochemical processes in this system. Talar c...
This study demonstrates for the first time that human articular chondrocytes express osteogenic protein-1 (OP-1). OP-1 was originally purified from bone matrix and was shown to induce cartilage and bone formation. Both OP-1 protein and message were present in human normal and osteoarthritic (OA) cartilages. OP-1 mRNA was upregulated in OA cartilage...
Successful and cartilage-specific cultivation of chondrocytes requires a stable phenotype during the in vitro culture period. This is based on a differentiated extracellular matrix synthesis. The alginate system as a three-dimensional support is a useful system to culture chondrocytes and to analyze the biochemical processes in this system. Talar c...
Objective
To determine the effects of osteogenic protein 1 (OP-1) on hyaluronan (HA), CD44, and aggrecan biosynthesis as well as the contribution of these molecules in promoting matrix assembly by human articular chondrocytes.Methods
Normal human chondrocytes were cultured with or without OP-1 treatment. Changes in the relative expression of messen...
The objectives of this study were the following: (a) describe the appearance of histopathologic changes observed in human articular cartilage from the knee and ankle joints of organ donors with no symptomatic joint disease; (b) compare by in situ hybridization mRNA expression of six matrix metalloproteinases (MMP) in these cartilages; (c) compare M...
Hyaluronic acid, recently renamed hyaluronan, has been used as a therapeutic intervention in the treatment of osteoarthritis. We have reported that high-molecular-weight (800 kDa) hyaluronan is effective in blocking the catabolic action of fibronectin fragments in explant cultures of bovine cartilage and in an experimental in vivo model of damage t...
The abilities of osteogenic protein-1 (OP-1) and TGF-beta1 to affect cartilage damage caused by fibronectin fragments (Fn-fs) that are known to greatly enhance cartilage proteoglycan (PG) degradation were compared.
Articular cartilage was obtained from 18 month old bovines.
To test blocking of damage, cartilage was cultured with or without OP-1 or...
We have performed cDNA sequencing and homology analyses to elucidate the complete amino acid composition for a superficial zone protein (SZP) from human and bovine cartilage which has previously been shown to be a proteoglycan specifically synthesized by chondrocytes located at the surface of bovine articular cartilage and also some synovial lining...
The prevalence of osteoarthritis (OA) is higher in some joints than in others. Fibrillation and full-thickness cartilage defects in the knee have been considered to be evidence of developing OA (pre-OA). While similar changes have been reported in the ankle (talocrural joint), the frequency of these changes is much higher than expected if the degen...
Synovial (diarthrodial) joints facilitate mobility by allowing bones to articulate with one another. In synovial joints, the bones are covered by hyaline articular cartilage: a viscoelastic tissue that cushions and thus minimizes the forces that the non-deformable bones are subjected to during load bearing. Each synovial joint contains a vasculariz...
We have previously described a large proteoglycan named superficial zone protein that was isolated and purified from culture medium of superficial slices of bovine articular cartilage. Monoclonal antibodies were raised against superficial zone protein and used as probes in Western blot analyses for immunohistochemical studies both to determine prec...
According to numerous cadaveric, radiographic, and clinical studies, ankle and knee joints differ in susceptibility to osteoarthritis. To test for biochemical differences in susceptibility to damage, a chondrocytic chondrolysis system has been utilized. In this system, fibronectin fragments are added to cultured cartilage explants, resulting in enh...
The depletion of the pericellular and territorial matrices in articular cartilage is considered to be one of the earliest events in pathobiology of osteoarthritis (OA). A newly discovered family of proteins with a disintegrin-like and metalloproteinase-like domain (ADAM) may be involved in matrix degradation as well as in cell-cell and cell-matrix...
Recombinant human osteogenic protein 1 (OP-1) is an effective stimulator of human cartilage 35S-proteoglycan synthesis. The present study was conducted to determine whether stimulation of human articular chondrocytes with OP-1 can help overcome interleukin-1beta (IL-1beta)-induced suppression of 35S-proteoglycan synthesis.
Human articular chondrocy...
Objective. Recombinant human osteogenic protein 1 (OP-1) is an effective stimulator of human cartilage 35S-proteoglycan synthesis. The present study was conducted to determine whether stimulation of human articular chondrocytes with OP-1 can help overcome interleukin-1β (IL-1β)-induced suppression of 35S-proteoglycan synthesis.
Methods. Human artic...
Although there is sparse information concerning the properties of foot-joint cartilages, knowledge of the morphology and biochemistry of these cartilages is important in the study of changes that occur in the development of osteoarthritis. Normal first and fifth metatarsophalangeal joints were chosen for comparison because of the difference between...
A commercial preparation of 800-kDa hyaluronic acid (HA), (ARTZ from Seikagaku, Inc.), has been used as a therapeutic intervention in the treatment of osteoarthritis (OA). We tested the effect of this HA form, HA/800, in an in vitro cartilage chondrolytic system in which a specific amino-terminal 29-kDa fragment of fibronectin (Fn-f) penetrates car...
Intra-articular sodium hyaluronic acid (HA) has been used as a treatment intervention in the management of osteoarthritis. It has been observed that HA can coat the articular surface, and thus, has been suggested to provide a possible prophylactic barrier for the articular cartilage. In an accompanying manuscript (Homandberg et al.), we report that...
Cartilage oligomeric matrix protein (COMP) is a high-molecular-weight glycoprotein found at a high concentration in articular cartilage. Recent studies have shown that the joint fluid and serum levels of antigenic COMP, measured by an enzyme-linked immunosorbent assay (ELISA) which uses a polyclonal antiserum raised against bovine COMP, provide imp...
To detect the message for membrane type 1 (MT1) matrix metalloproteinase (MMP) in articular cartilage and chondrosarcoma cells, to study its expression in osteoarthritis (OA), and to determine whether interleukin-1beta (IL-1beta) influences its expression.
Reverse transcription-polymerase chain reaction methods were used to detect message. Cloning...
Ankle and knee joints differ in their susceptibility to osteoarthritis (OA). This article reviews literature on differences between these joints. A Medline search and search of bibliographies of review articles was conducted. Knee cartilage degeneration leads to the development of OA with clinical symptoms, whereas the ankle cartilage develops fiss...