Crucial role of synovial lining macrophages in the promotion of transforming growth factor beta-mediated osteophyte formation.

Crucial role of synovial lining macrophages in the promotion of transforming growth factor beta-mediated osteophyte formation. Research Abstract Details 

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Crucial role of synovial lining macrophages in the promotion of transforming growth factor beta-mediated osteophyte formation. Abstract Text:

P L E M van Lent,A B Blom,P van der Kraan,A E M Holthuysen,E Vitters,N van Rooijen,R L Smeets,K C A M Nabbe,W B van den Berg,

OBJECTIVE: To investigate in vivo and in vitro whether macrophages have an intermediate role in transforming growth factor beta (TGFbeta)-induced osteophyte formation. METHODS: In vivo, synovial lining macrophages were selectively depleted by injection of clodronate-laden liposomes 7 days prior to injection of 20 ng or 200 ng of TGFbeta 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 TGFbeta into normal murine knee joints induced significant osteophyte formation at the lateral and medial sites of the patella and femur on day 7 after the last injection. Strikingly, removal of synovial lining macrophages prior to TGFbeta injection resulted in a drastic reduction of osteophyte formation (by 70% and 64% after injection of 20 ng and 200 ng of TGFbeta, respectively). Synovial lining cells produced BMP-2 and BMP-4 after TGFbeta stimulation, whereas BMP-2 and BMP-4 were absent in the synovial tissue after macrophage depletion. In vitro, clustering and spheroid formation of C3H10T1/2 was induced by TGFbeta concentrations of >1 ng/ml. However, in the Transwell system, in the presence of murine macrophages, 0.5 ng/ml of TGFbeta was very effective in generating large spheroids, suggestive of macrophage-derived (co)factors. In coculture supernatants, TGFbeta concentrations were not elevated in the presence of macrophages, indicating generation of other growth factors involved in spheroid formation. CONCLUSION: These findings indicate that macrophages are crucial intermediate factors in osteophyte formation induced by TGFbeta, probably by inducing other chondrogenic signals.

Crucial role of synovial lining macrophages in the promotion of transforming growth factor beta-mediated osteophyte formation. Publishing Authors By Initials

PL van Lent,AB Blom,P van der Kraan,AE Holthuysen,E Vitters,N van Rooijen,RL Smeets,KC Nabbe,WB van den Berg,

For similar peptides: intercellular signaling peptides and proteins: cytokines: transforming growth factor beta research abstracts see: peptides: intercellular signaling peptides and proteins: cytokines: transforming growth factor beta research

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Crucial role of synovial lining macrophages in the promotion of transforming growth factor beta-mediated osteophyte formation. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: Arthritis and rheumatism

VOLUME: 50

Page Numbers: 103-11

Journal Abbreviation: Arthritis Rheum.

ISSN: 0004-3591

DAY: 19

MONTH: Jan

YEAR: 2004

Crucial role of synovial lining macrophages in the promotion of transforming growth factor beta-mediated osteophyte formation. Information

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LANGUAGE: eng

NlmUniqueID: 370605

Crucial role of synovial lining macrophages in the promotion of transforming growth factor beta-mediated osteophyte formation. Keywords Mesh Terms:

KEYWORDS: Transforming Growth Factor beta

MESH TERMS: pharmacology

Chemical & Substance for Abstract: Crucial role of synovial lining macrophages in the promotion of transforming growth factor beta-mediated osteophyte formation. Information

Substance Name: Clodronic Acid

Registry Number: 10596-23-3

Grant and Affiliation Information for Crucial role of synovial lining macrophages in the promotion of transforming growth factor beta-mediated osteophyte formation.

AFFILIATION: University Medical Center, Nijmegen, The Netherlands. P.vanLent@reuma.umcn.nl

Country: United States

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MEDLINETA: Arthritis Rheum

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