Incomplete elongation of the chondroitin sulfate linkage region on aggrecan and response to interleukin-1β.

Aggrecan is the prominent proteoglycan in cartilage and is modified with approximately 100 chondroitin sulfate (CS) chains through a tetrasaccharide linkage structure. In osteoarthritis (OA), the viscoelastic properties of cartilage are compromised on both the quantity and integrity of aggrecan core protein expressed as well as reduced overall CS chain length. Herein, we postulated that chronic low-level inflammation may also contribute to OA progression by promoting regulatory mechanisms in early CS biosynthesis that yield incomplete linkage structures on aggrecan.

Post-traumatic osteoarthritis: improved understanding and opportunities for early intervention.

Even with current treatments of acute joint injuries, more than 40% of people who suffer significant ligament or meniscus tears, or articular surface injuries, will develop osteoarthritis (OA). Correspondingly, 12% or more of all patients with lower extremity OA have a history of joint injury. Recent research suggests that acute joint damage that occurs at the time of an injury initiates a sequence of events that can lead to progressive articular surface damage.

Protective effect of P188 in the model of acute trauma to human ankle cartilage: the mechanism of action.

Objective: Because P188 poloxamer is effective in promoting cell survival in models of acute trauma, the objectives were to understand the mechanism of its action focusing on glycogen synthase kinase-3 (GSK3) activation, interleukin-6 (IL-6), and p38 signaling.

Design: Sixteen normal human tali were impacted using a 4-mm diameter indenter with an impulse of 1 Ns. Eight-millimeter cartilage plugs containing the 4-mm impacted core and 4-mm adjacent nonimpacted ring were removed and cultured with or without P188.

Mactinin, a fragment of cytoskeletal alpha-actinin, is a novel inducer of heat shock protein (Hsp)-90 mediated monocyte activation.

Background: Monocytes, their progeny such as dendritic cells and osteoclasts and products including tumor necrosis factor (TNF)-alpha, interleukin (IL)-1alpha and IL-1beta play important roles in cancer, inflammation, immune response and atherosclerosis. We previously showed that mactinin, a degradative fragment of the cytoskeletal protein alpha-actinin, is present at sites of monocytic activation in vivo, has chemotactic activity for monocytes and promotes monocyte/macrophage maturation. We therefore sought to determine the mechanism by which mactinin stimulates monocytes.

Cell therapy using articular chondrocytes overexpressing BMP-7 or BMP-10 in a rabbit disc organ culture model.

Study Design: Rabbit knee articular chondrocytes overexpressing human growth factors were injected into cultured intervertebral disc explants. Survival of the injected cells and accumulation of extracellular matrix were assessed.

Objective: To define the utility of cell-based gene delivery approach for repair of the intervertebral disc.

Mactinin treatment promotes wound-healing-associated inflammation in urokinase knockout mice.

Mactinin, a 31 kDa fragment from the amino-terminal end of alpha-actinin, is chemotactic for monocytes and can promote monocyte/macrophage maturation. Macrophages are essential for wound healing, in which they play key roles in debridement, angiogenesis, fibroblast proliferation, and collagen metabolism. We have previously determined that urokinase is necessary to form mactinin from extracellular alpha-actinin, which may be present at sites of inflammation as a result of cell movement.

Growth factors and treatment of intervertebral disc degeneration.

Study Design: Literature review.

Objective: To review the most recent findings of the effects of growth factors on the intervertebral disc and, further, to discuss trends in the biologic repair of the degenerated intervertebral disc.

Summary Of Background Data: Since early in 1990, advancements in molecular biology and cell culture technology have enabled researchers to accumulate knowledge about the in vitro actions of growth factors on intervertebral disc cells.

The effects of displacement rate and proteoglycan digestion on the fracture resistance of tissue grown from chondrocyte culture.

Fracture toughness of cartilage and cartilage replacement tissues is important in injury and disease. For example, cartilage is thought to weaken before it fibrillates in the disease osteoarthritis. Since both loading rate and proteoglycan content affect viscoelastic properties, they may both affect fracture toughness of cartilage and cartilage analogs.

Differential gene expression in ovarian carcinoma: identification of potential biomarkers.

Ovarian cancer remains the fifth leading cause of cancer death for women in the United States. In this study, the gene expression of 20 ovarian carcinomas, 17 ovarian carcinomas metastatic to the omentum, and 50 normal ovaries was determined by Gene Logic Inc. using Affymetrix GeneChip HU_95 arrays containing approximately 12,000 known genes.

Ovarian carcinoma ascites spheroids adhere to extracellular matrix components and mesothelial cell monolayers.

Objectives: Ovarian carcinoma cells form multicellular aggregates, or spheroids, in the peritoneal cavity of patients with advanced disease. The current paradigm that ascites spheroids are non-adhesive leaves their contribution to ovarian carcinoma dissemination undefined. Here, spheroids obtained from ovarian carcinoma patients' ascites were characterized for their ability to adhere to molecules encountered in the peritoneal cavity, with the goal of establishing their potential to contribute to ovarian cancer spread.

The effect of exogenous glucosamine hydrochloride on the proteoglycan concentration of the articular disc of the rabbit temporomandibular joint.

Aims: To test the effect of glucosamine hydrochloride (glucosamine-HCl) on the proteoglycan (PG) concentration of the articular disc of non-arthritic temporomandibular joints (TMJs) in rabbits.

Methods: Twenty-four of 48 New Zealand white 10- to 12-week-old male rabbits (2.2 kg average) were injected with the irritant chymopapain in the knee joint.

Mactinin: a modulator of the monocyte response to inflammation.

During inflammatory processes, monocytes leave the blood stream at increased rates and enter inflammation tissue, where they undergo phenotypic transformation to mature macrophages with enhanced phagocytic activity. alpha-Actinin, a cytoskeletal protein, is present in focal adhesion complexes and left in the microenvironment as a result of cell movement. Mactinin, a 31 kDa amino-terminal fragment of alpha-actinin, is generated by the degradation of extracellular alpha-actinin by monocyte-secreted urokinase.

Cell death after cartilage impact occurs around matrix cracks.

The damage from rapid high energy impacts to cartilage may contribute to the development of osteoarthritis (OA). Understanding how and when cells are damaged during and after the impact may provide insight into how these lesions progress. Mature bovine articular cartilage on the intact patella was impacted with a flat impacter to 53 MPa in 250 ms.

Establishment of an in vitro assay to measure the invasion of ovarian carcinoma cells through mesothelial cell monolayers.

Ovarian carcinoma is the leading cause of gynecological cancer deaths in the United States. Secondary tumor growths form by tumor cell invasion through the mesothelial lining of the peritoneal cavity and peritoneal organs. To study this interaction, we developed a dye-based in vitro model system in which mesothelial cells were grown as confluent monolayers, permeabilized, and then co-cultured with ovarian carcinoma cells for up to seven days.

Cell membrane glycosylation mediates the adhesion, migration, and invasion of ovarian carcinoma cells.

We have previously shown that ovarian carcinoma cell adhesion to mesothelial cell monolayers and migration toward fibronectin, type IV collagen, and laminin is partially mediated by CD44, a proteoglycan known to affect the functional abilities of tumor cells. The purpose of this study was to determine the role of cell membrane glycosylation in the metastatic abilities of ovarian carcinoma cells. NIH:OVCAR5 cells were treated with glycosidases to remove carbohydrate moieties from molecules on the cells' surface.

Effect of oral glucosamine on cartilage and meniscus in normal and chymopapain-injected knees of young rabbits.

Objective: To determine if oral glucosamine (GlcN) improves joint biology after acute damage by a protease.

Methods: The effect of 8 weeks of dietary GlcN (20 or 100 mg/kg/day) on knee joint cartilage was evaluated in 2.2-kg male NZW rabbits with and without damage introduced by intraarticular injection of chymopapain (CP).

Urokinase is required for the formation of mactinin, an alpha-actinin fragment that promotes monocyte/macrophage maturation.

We have previously shown that lysates from HL-60 myeloid leukemia cells or from peripheral blood monocytes are able to degrade alpha-actinin to form a 31-kDa amino-terminal fragment with monocyte/macrophage maturation promoting activity. In contrast, intact alpha-actinin, which is a 100-kDa actin-binding protein, has no differentiating activity. The aim of this study was to investigate the enzyme responsible for the degradation of alpha-actinin to form this fragment, named mactinin.

Manipulation of hyaluronan synthase expression in prostate adenocarcinoma cells alters pericellular matrix retention and adhesion to bone marrow endothelial cells.

Prostate cancer metastasis to bone marrow involves initial adhesion of tumor cells to the bone marrow endothelium, followed by transmigration and proliferation within the marrow. Rapid, specific adhesion of highly metastatic prostate adenocarcinoma cells (PC3M-LN4) to bone marrow endothelial cell (BMEC) lines requires a pericellular hyaluronan (HA) matrix and correlates with dramatically up-regulated HA synthase (HAS) expression. Non-metastatic prostate tumor cells (LNCaP) do not assemble a HA matrix, adhere poorly to BMECs, and express normal levels of HAS.

Prostaglandins and the Zone of Calcified Cartilage in Osteoarthritis.

The zone of calcified cartilage (ZCC) which provides the critical interface between cartilage and bone acts as the growth plate in the developing joint. In osteoarthritis, it has been hypothesized that the ZCC may again function in joint remodeling. This could result in thinning of the cartilage.