Inflammation has been associated with early degradative changes in articular cartilage and immune responses are key factor influencing normal tissue regeneration and repair. With synovitis a prominent feature in osteoarthritis (OA) and associated with the progressive degradation of articular cartilage, immune factors need to be factored into efforts to achieve efficient cartilage repair/regeneration. Recent efforts have focused on the use of autologous or allogeneic mesenchymal stem/stromal cells (MSCs) to modulate the inflammatory environment in the injured or osteoarthritic joint. Intraarticular injection of MSCS has modulated cartilage degradation in a variety of pre-clinical OA models. Results from early clinical trials have also shown effects on pain and function-associated outcome measures. Other cell types may also have some capacity for use as a therapy for OA. For example, primary allogeneic chondrocytes also seem to have some immune-privilege in the synovial joint and are immunomodulatory in a rat model. Although MSCs isolated from bone marrow that are induced to undergo chondrogenic differentiation do not retain these properties, MSCs isolated from the synovium or chondroprogenitors generated from cartilage itself may represent the future of cell therapy for OA

Summary. Hyaluronan suppressed lipopolysaccharide-stimulated prostaglandin E. 2. production via intercellular adhesion molecule-1 through down-regulation of nuclear factor-κB. Administration of hyaluronan into rheumatoid joints may decrease prostaglandin E. 2. production by activated macrophages, which could result in improvement of arthritic pain. Introduction. Prostaglandin E. 2. (PGE. 2. ) is one of the key mediators of inflammation in rheumatoid arthritis (RA) joints. Intra-articular injection of high molecular weight hyaluronan (HA) into RA knee joints relieves arthritic pain. Although HA has been shown to inhibit PGE. 2. production in cytokine-stimulated synovial fibroblasts, it remains unclear how HA suppresses PGE. 2. production in catabolically activated cells. Furthermore, HA effect on macrophages has rarely been investigated in spite of their contribution to RA joint pathology. Objectives. This study was aimed to investigate the inhibitory mechanism of HA on lipopolysaccharide (LPS)-stimulated PGE. 2. in U937 human macrophage culture system. Methods. With or without pretreatment with one of HA, NS-398, and BAY11-7085, differentiated U937 macrophages were stimulated with LPS. In another set of experiments, the cells were incubated with anti-ICAM-1 antibody or non-specific IgG before pretreatment with HA. PGE. 2. concentrations of the cell-free supernatants were determined using an enzyme-linked immunosorbent assay. The cell lysates and nuclear extracts were prepared for immunoblot analysis. HA binding to ICAM-1 was evaluated by fluorescence microscopic analysis. Results. Stimulation of U937 macrophages with LPS enhanced PGE. 2. production in association with increased protein levels of cyclooxygenase-2 (COX-2). Pretreatment with HA of 2,700 kDa resulted in suppression of LPS-induced COX-2, leading to a decrease in PGE. 2. production. While LPS activated NF-κB pathway, inhibition studies using BAY11-7085 revealed the requirement of NF-κB for LPS-stimulated PGE. 2. production. HA down-regulated the phosphorylation and nuclear translocation of NF-κB by LPS. Fluorescence cytochemistry demonstrated that HA bound to ICAM-1 on U937 macrophages. Anti-ICAM-1 antibody reversed the inhibitory effects of HA on LPS-activated PGE. 2. , COX-2, and NF-κB. Conclusion. These results clearly demonstrated that HA suppressed LPS-stimulated PGE2 production via ICAM-1 through down-regulation of NF-κB. Clinical administration of high molecular weight HA into RA joints may decrease PGE2 production by activated macrophages, which could result in improvement of arthritic pain

Objectives

The role of mechanical stress and transforming growth factor beta 1 (TGF-β1) is important in the initiation and progression of osteoarthritis (OA). However, the underlying molecular mechanisms are not clearly known.

Objectives

We studied subchondral intraosseous pressure (IOP) in an animal model during loading, and with vascular occlusion. We explored bone compartmentalization by saline injection.

Objectives

Triamcinolone acetonide (TA) is widely used for the treatment of rotator cuff injury because of its anti-inflammatory properties. However, TA can also produce deleterious effects such as tendon degeneration or rupture. These harmful effects could be prevented by the addition of platelet-rich plasma (PRP), however, the anti-inflammatory and anti-degenerative effects of the combined use of TA and PRP have not yet been made clear. The objective of this study was to determine how the combination of TA and PRP might influence the inflammation and degeneration of the rotator cuff by examining rotator cuff-derived cells induced by interleukin (IL)-1ß.

We produced large full-thickness articular cartilage defects in 33 rabbits in order to evaluate the effect of joint distraction and autologous culture-expanded bone-marrow-derived mesenchymal cell transplantation (ACBMT) at 12 weeks. After fixing the knee on a hinged external fixator, we resected the entire surface of the tibial plateau. We studied three groups: 1) with and without joint distraction; 2) with joint distraction and collagen gel, and 3) with joint distraction and ACBMT and collagen gel.

The histological scores were significantly higher in the groups with ACBMT collagen gel (p < 0.05). The area of regenerated soft tissue was smaller in the group allowed to bear weight (p < 0.05). These findings suggest that the repair of large defects of cartilage can be enhanced by joint distraction, collagen gel and ACBMT.