Onset of preclinical osteoarthritis: the angular spatial organization permits early diagnosis.

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 between a chondrocyte and its surrounding neighbors, we compared maturational and degenerative changes of the cellular organizations in rat and human cartilage specimens.

Vulnerability of the superficial zone of immature articular cartilage to compressive injury.

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 by injury.

Proliferative remodeling of the spatial organization of human superficial chondrocytes distant from focal early osteoarthritis.

Objective: 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.

Methods: Samples of intact cartilage (condyles, patellofemoral groove, and proximal tibia) lying distant from focal lesions of OA in grade 2 joints were compared with location-matched nondegenerative (grade 0-1) cartilage samples.

Distinct horizontal patterns in the spatial organization of superficial zone chondrocytes of human joints.

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-degenerated superficial zone of articular cartilage is not available for most human joints. The present study analyzed the arrangement of chondrocytes of non-degenerated human joints (shoulder, elbow, knee, and ankle) by using fluorescence microscopy of the superficial zone in a top-down view.

Analysis of the relationship between peak stress and proteoglycan loss following injurious compression of human post-mortem knee and ankle cartilage.

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 knee and ankle cartilages.

Collagen and proteoglycan turnover in focally damaged human ankle cartilage: evidence for a generalized response and active matrix remodeling across the entire joint surface.

Objective: 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.

Methods: Cartilage samples were obtained from the tali of normal ankles and from 3 sites on tali with lesions (the lesion, adjacent to the lesion, and far removed from the lesion).

Reliability of diffraction enhanced imaging for assessment of cartilage lesions, ex vivo.

Objective: 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 radiographic imaging technique. DEI provides two new sources of image contrast to radiography: refraction and scatter rejection, besides the absorption of conventional radiography.

Antisense inhibition of osteogenic protein 1 disturbs human articular cartilage integrity.

Objective: 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.

Methods: 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 alginate or high-density monolayers for 48 hours in the presence of OP-1 antisense or sense oligonucleotides.

Differential matrix degradation and turnover in early cartilage lesions of human knee and ankle joints.

Objective: 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.

Methods: Cartilage removed from lesions of the tali and femoral condyles was analyzed for type IIB collagen messenger RNA, C-terminal type II procollagen propeptide (CPII), the collagenase cleavage neoepitope (Col2-3/4C(short)), and the denaturation epitope (Col2-3/4m). The content of collagen, glycosaminoglycan, and epitope 846 of aggrecan was quantitated.

Radiography of soft tissue of the foot and ankle with diffraction enhanced imaging.

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 imaging technique that could detect both bone and soft tissues seemed unrealistic.

X-ray detection of structural orientation in human articular cartilage.

Objective: To determine the feasibility of detecting the structural orientation in cartilage with Diffraction Enhanced X-Ray Imaging.

Design: 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 monochromatic and highly collimated beam, with an analyzer crystal that selectively weights out photons according to the angle they have been deviated with respect to the original direction.

Modulation of endogenous osteogenic protein-1 (OP-1) by interleukin-1 in adult human articular cartilage.

Background: 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.

Methods: Normal adult human articular cartilage explants were cultured for twenty-five days in the presence of medium only or were treated with a low dose (0.

Alterations in endogenous osteogenic protein-1 with degeneration of human articular cartilage.

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 to investigate both qualitatively and quantitatively endogenous OP-1 in normal, degenerative, and OA cartilage.

Distinguishing ankle and knee articular cartilage.

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 ankle were more severe in men than in women, were predominantly bilateral, and seemed to be correlated with weight.

Regulation of osteogenic proteins by chondrocytes.

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 cartilage physiology and BMPs, we analyze the data on the role of recombinant BMPs as anabolic agents in tissue formation and restoration in different in vitro and in vivo models following with the endogenous expression of BMPs and factors that regulate their expression.

Radiography of soft tissue of the foot and ankle with diffraction enhanced imaging.

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 imaging technique that could detect both bone and soft tissues seemed unrealistic.

Radiography of rabbit articular cartilage with diffraction-enhanced imaging.

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-ray imaging technique that could detect both the degenerative cartilage and bone features of joint diseases is of special interest.

Matrix homeostasis in aging normal human ankle cartilage.

Objective: To study age-related (as opposed to arthritis-related) changes in collagen and proteoglycan turnover.

Methods: 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 (CPII), to the type II collagen (CII) collagenase-generated cleavage neoepitope (Col2-3/4C(short)), and to the CII denaturation product (Col2-3/4m) were used for immunohistochemistry analysis and immunoassay. In addition, immunoblotting was used to detect the 4 collagenases.

Age-related changes in cartilage endogenous osteogenic protein-1 (OP-1).

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.

Immunohistochemical localization of osteogenetic protein (OP-1) and its receptors in rabbit articular cartilage.

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 receptors was also examined in cartilage from joints that had been previously subjected to cartilage matrix degradation. Pro-OP-1 was moderately expressed in chondrocytes of the superficial, middle, and deep cartilage zones and in the osteocytes.

Human knee and ankle cartilage explants: catabolic differences.

The prevalence of osteoarthritis (OA) is lower in some joints, i.e., the ankle, than in the knee.

Horizontally oriented clusters of multiple chondrons in the superficial zone of ankle, but not knee articular cartilage.

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.

Evidence of an Eicosanoid Contribution to IL-1 Induction of IL-6 in Human Articular Chondrocytes.

It has been demonstrated previously that interleukin-1 (IL-1) induces articular cartilage explants and chondrocytes in culture to produce elevated levels of inflammatory mediators such as interleukin-6 (IL-6) and prostaglandins. Previous studies have also demonstrated a relationship between IL-6 secretion and the ability of IL-1 to modulate proteoglycan synthesis by chondrocytes. In this study we have utilized an alginate culture system in an effort to investigate a role for eicosanoids in IL-1 induction of IL-6 expression in human articular chondrocytes.