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Objective. Prostaglandin E 2 (PGE 2 ) is one of the main catabolic factors involved in osteoarthritis (OA), and metalloproteinases (MMPs) are crucial for cartilage degradation. PGE 2 synthesis under inflammatory conditions is catalyzed by cyclooxygenase 2 and microsomal PGE synthase 1 (mPGES-1), whereas NAD؉-dependent 15-hydroxy-PG dehydrogenase (15-PGDH) is the key enzyme implicated in PGE 2 catabolism. The present study was undertaken to investigate the contribution of visfatin, an adipose tissue-derived hormone, to the pathophysiology of OA, by examining its role in PGE 2 synthesis and matrix degradation. Osteoarthritis (OA) causes pain and dysfunction and is the leading cause of disability in elderly people in industrialized countries (1). It results in breakdown of articular cartilage with concomitant changes in the underlying bone, development of osteophytes, and some degree of synovial inflammation (2). The extracellular matrix of cartilage is destroyed and the phenotype of chondrocytes altered due to changes in their pattern of gene expression. They lose their differentiated phenotype and undergo focal cell death and degeneration (3). Several epidemiologic studies have shown a positive

A high-resolution CT system using synchrotron radiation allowed visualization of the 3D cortical bone microarchitecture and measurement of intracortical porosity of femoral neck cortical bone specimens from 19 female cadavers imaged at 10.13-m resolution. 3D reconstruction of specimens showed osteonal system arrangement. Mean porosity was 15.88%. This technique will provide insights into the mechanisms involved in osteoporotic hip fractures.Introduction: The purpose of this study was to show that a high-resolution CT system using synchrotron radiation (SR) allows visualization of the 3D cortical bone microarchitecture of the human femoral neck and quantification of intracortical porosity. Materials and Methods: Bone specimens from the inferior femoral neck were obtained from 19 female cadavers with no hip fracture (mean, 86.9 Ϯ 8.3 years). The specimens, consisting of embedded ϳ7 ϫ 7 ϫ 12-mm cortical bone parallelepipeds, were imaged using SR at 10.13-m resolution. Commercial software was used to visualize both the 660 ϫ 660 ϫ 660-voxel volumes and the 2D axial slices through each volume. Qualitative examination of 2D axial slices focused on the appearance of the vessel canal system, presence of small bright zones (fully mineralized tissue) in the osseous matrix, and presence of cracks. A method was developed to automatically measure 3D intracortical porosity after separating pure bone from pores and cortical bone from trabecular bone. Results and Conclusions: 3D reconstruction of the specimens showed the entire structure and arrangement of the osteonal systems, parallel to the axis of the femoral neck. Bright zones were seen in the outer cortex. No cracks were observed. Porosity values varied widely from 4.96% to 38.87% (mean, 15.88 Ϯ 9.87%). This study establishes that SR microtomography can be used to display the 3D bone microstructure of the human femoral neck cortex and to quantify intracortical porosity. This technique will provide insights into the mechanisms involved in cortical bone loss and osteoporotic hip fractures.

OA cartilages from DM patients showed increased responsiveness to IL-1β-induced inflammation. Accordingly, high glucose enhanced IL-1β-induced inflammation in cultured chondrocytes via oxidative stress and the polyol pathway. High glucose and diabetes may thus participate in the increased inflammation in OA.

IntroductionVisfatin is an adipokine that may be involved in intertissular joint communication in osteoarthritis (OA). With a homodimeric conformation, it exerts nicotinamide phosphoribosyltransferase (Nampt) enzymatic activity, essential for nicotinamide adenine dinucleotide biosynthesis. We examined the tissular origin and conformation of visfatin/Nampt in human OA joints and investigated the role of visfatin/Nampt in chondrocytes and osteoblasts by studying Nampt enzymatic activity.MethodsSynovium, cartilage and subchondral bone from human OA joints were used for protein extraction or incubated for 24 hours in serum-free media (conditioned media), and synovial fluid was obtained from OA patients. Visfatin/Nampt expression in tissular extracts and conditioned media was evaluated by western blot and enzyme-linked immunosorbent assay (ELISA), respectively. Nampt activity was assessed in OA synovium by colorimetric assay. Primary cultures of murine chondrocytes and osteoblasts were stimulated with visfatin/Nampt and pretreated or not with APO866, a pharmacologic inhibitor of Nampt activity. The effect on cytokines, chemokines, growth factors and hypertrophic markers expression was examined by quantitative reverse transcriptase polymerase chain reaction and/or ELISA.ResultsIn tissular explants, conditioned media and synovial fluid, visfatin/Nampt was found as a homodimer, corresponding to the enzymatically active conformation. All human OA joint tissues released visfatin/Nampt (synovium: 628 ± 106 ng/g tissue; subchondral bone: 195 ± 26 ng/g tissue; cartilage: 152 ± 46 ng/g tissue), with significantly higher level for synovium (P <0.0005). Nampt activity was identified ex vivo in synovium. In vitro, visfatin/Nampt significantly induced the expression of interleukin 6, keratinocyte chemoattractant and monocyte chemoattractant protein 1 in chondrocytes and osteoblasts. APO866 decreased the mRNA and protein levels of these pro-inflammatory cytokines in the two cell types (up to 94% and 63% inhibition, respectively). Levels of growth factors (vascular endothelial growth factor, transforming growth factor β) and hypertrophic genes were unchanged with treatment.ConclusionVisfatin/Nampt is released by all human OA tissues in a dimeric enzymatically active conformation and mostly by the synovium, which displays Nampt activity. The Nampt activity of visfatin is involved in chondrocyte and osteoblast activation, so targeting this enzymatic activity to disrupt joint tissue interactions may be novel in OA therapy.

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These results demonstrate that ASU express a unique range of activities, which could counteract deleterious processes involved in OA, such as inflammation.