Inflammation and angiogenesis in osteoarthritis

Abstract

Objective. To quantify the relationship between inflammation and angiogenesis in synovial tissue from patients with osteoarthritis (OA).Methods. Hematoxylin and eosin staining and histologic grading for inflammation were performed for 104 patients who met the American College of Rheumatology criteria for OA and had undergone total joint replacement or arthroscopy. A purposive sample of synovial specimens obtained from 70 patients was used for further analysis. Vascular endothelium, endothelial cell (EC) proliferating nuclei, macrophages, and vascular endothelial growth factor (VEGF) were detected by immunohistochemical analysis. Angiogenesis (EC proliferation, EC fractional area), macrophage fractional area, and VEGF immunoreactivity were measured using computer-assisted image analysis. Double immunofluorescence histochemical analysis was used to determine the cellular localization of VEGF. Radiographic scores for joint space narrowing and osteophyte formation in the knee were also assessed.Results. Synovial tissue samples from 32 (31%) of 104 patients with OA showed severe inflammation; thickened intimal lining and associated lymphoid aggregates were often observed. The EC fractional area, EC proliferation, and VEGF immunoreactivity all increased with increasing histologic inflammation grade and increasing macrophage fractional area. In the synovial intimal lining, VEGF immunoreactivity was localized to macrophages and increased with increasing EC fractional area and angiogenesis. No inflammation or angiogenic indices were significantly correlated with radiographic scores.

Intraarticular gene transfer of thrombospondin‐1 suppresses the disease progression of experimental osteoarthritis

“…8,18 Angiogenesis and inflammation in synovial tissue are highly associated with osteoarthritis. 4,19 Synovium is important for maintaining the health of joints. During disease progression, infiltrated macrophages within the synovial membrane produce angiogenic factors, such as vascular endothelial growth factor (VEGF), cytokines, and lowmolecular weight factors, and they impair homeostasis of the articular cartilage.…”

“…3 Furthermore, vascular growth is also higher in the synovium from patients with than without osteoarthritis and is associated with synovitis. 4 Osteochondral angiogenesis facilitates the progression of osteoarthritis. 5 Angiogenesis and inflammation interact and mutually affect each other in the osteoarthritic joint.…”

Angiogenesis and the persistence of inflammation in a rat model of proliferative synovitis

“…Synovial angiogenesis is also a feature of chronic synovitis in both humans and animals (30,47,48). In the present study, we demonstrated increased EC proliferation during chronic synovitis 29 days after coinjection of carrageenan and FGF-2.…”

Immune Modulation to Improve Tissue Engineering Outcomes for Cartilage Repair in the Osteoarthritic Joint

“…40 VEGF is expressed by macrophages and known to induce endothelial cell chemotaxis and mediating vascular permeability, an important process in inflammation. [77][78][79] Interestingly, intra-articular injection of VEGF in mice has increased calcification of AC, cartilage degradation, and subchondral bone sclerosis, implicating a role of VEGF in OA. 80 ICAM-1 is upregulated by osteoarthritic synoviocytes in response to pro-inflammatory stimuli and plays an important role in transendothelial migration of T cells and may therefore mediate the migration and infiltration of lymphocytes in the synovium.…”