Arthritis & Rheumatism, Volume 60,
October 2009 Abstract Supplement
The 2009 ACR/ARHP Annual Scientific Meeting
Philadelphia October 16-21, 2009.
R-Spondin1 Protects against Bone Loss During Murine Arthritis by Modulating the Wnt Pathway
Kronke1, Gerhard, Uderhardt1, Stefan, Kim2, Kyung-Ah, Schett1, Georg, Abo2, Arie
To test the efficiacy of the secreted Wnt modulator R-Spondin-1 (RSpo-1) in the preservation of joint integrity in a murine model of arthritis
RSpo-1 was applied to isolated osteoblasts and osteoclast/osteoblast co-cultures to evaluate its effect on the differentiation of these celltypes in vitro. To test the potency of RSpo-1 as a joint preserving agent in vivo, arthritic TNF-transgenic mice were treated with recombinant RSpo-1 by daily subcutaneous injection.
RSpo1 was highly effective in preserving structural integrity of joints in the TNF transgenic mouse model of rheumatoid arthritis by protecting bone and cartilage from inflammatory damage. RSpo1 antagonized the Wnt inhibitor Dkk1 and modulates Wnt signaling in mesenchymal cells. In osteoblasts RSpo1 induced differentiation and expression of OPG thereby inhibiting osteoclastogenesis in vitro. In joints, RSpo1 blocked osteoclast development and globally modulated the homeostasis of anabolic and catabolic gene expression. We observed induction of genes involved in both chondrogenesis and osteogenesis, which contributed to the integrity of cartilage and bone during joint inflammation.
Our results demonstrate the therapeutic potential of RSpo1 as an anabolic agent for the preservation of joint architecture.
To cite this abstract, please use the following information:
Kronke, Gerhard, Uderhardt, Stefan, Kim, Kyung-Ah, Schett, Georg, Abo, Arie; R-Spondin1 Protects against Bone Loss During Murine Arthritis by Modulating the Wnt Pathway [abstract]. Arthritis Rheum 2009;60 Suppl 10 :673