Crucial role of synovial lining macrophages in the promotion of transforming growth factor β–mediated osteophyte formation

P Van Lent, AB Blom, P Van Der Kraan… - … : Official Journal of …, 2004 - Wiley Online Library
P Van Lent, AB Blom, P Van Der Kraan, AEM Holthuysen, E Vitters, N Van Rooijen
Arthritis & Rheumatism: Official Journal of the American College …, 2004Wiley Online Library
Objective. To investigate in vivo and in vitro whether macrophages have an intermediate
role in transforming growth factor ß (TGFß)–induced osteophyte formation. Methods. In vivo,
synovial lining macrophages were selectively depleted by injection of clodronateladen
liposomes 7 days prior to injection of 20 ng or 200 ng of TGFß into murine knee joints 3
times, on alternate days. Total knee joint sections were obtained on day 7 after the last
injection and stained with Safranin O. Production of bone morphogenetic protein 2 (BMP-2) …
Objective. To investigate in vivo and in vitro whether macrophages have an intermediate role in transforming growth factor ß (TGFß)–induced osteophyte formation.
Methods. In vivo, synovial lining macrophages were selectively depleted by injection of clodronateladen liposomes 7 days prior to injection of 20 ng or 200 ng of TGFß into murine knee joints 3 times, on alternate days. Total knee joint sections were obtained on day 7 after the last injection and stained with Safranin O. Production of bone morphogenetic protein 2 (BMP-2) and BMP-4 was determined by immunolocalization. The interaction between murine macrophages and mesenchymal cells (precursors with chondrogenic potential) was studied in vitro using a Transwell system in which RAW macrophages were cocultured with C3H10T1/2 mesenchymal cells. Spheroid neocartilage formation was quantified microscopically after staining with May-Grünwald–Giemsa.
Results. Triple injections of 20 ng or 200 ng of
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