SOX11 contributes to the regulation of GDF5 in joint maintenance

BMC Developmental Biology

Clifford J Tabin¹  Hiroshi Kawaguchi²  Ung-il Chung³  Kozo Nakamura²  Takumi Nakagawa²  Atsushi Fukai²  Toshiyuki Ikeda²  Akinori Kan² 

[1] Department of Genetics, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA, 02115, USA;Sensory & Motor System Medicine, Faculty of Medicine, University of Tokyo, Hongo 7-3-1, Bunkyo, Tokyo 113-8655, Japan;Bone & Cartilage Regeneration, Faculty of Medicine, University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo, 113-8655, Japan

关键词: Articular cartilage;    Joint maintenance;    GDF5;    SOX11;   

Others  :  1086084
DOI  :  10.1186/1471-213X-13-4

 received in 2012-11-04, accepted in 2013-01-17,  发布年份 2013

【 摘 要 】

Background

Individual skeletal elements of the vertebrate limbs arise through a segmentation process introducing joints in specific locations. However, the molecular pathways controlling joint formation and subsequent joint maintenance are largely unknown. In this study, we focused on SOX11, and its contribution to the regulation of GDF5, a secreted signal necessary for proper joint formation and postnatal joint homeostasis.

Results

Sox11 is initially expressed broadly in the murine cartilage condensations at early stages of skeletal development, but its expression is specifically increased in the forming joint interzone as is forms. SOX11 overexpression can directly activate GDF5 expression both in vitro and in micromass cell cultures prepared from chick limb buds. Conserved SOX family binding sites are present in the 5’ UTR region of the GDF5 gene and we show SOX11 can specifically bind to one of them. While misexpression of Sox11 in developing chick limbs through RCAS virus infection does not induce Gdf5 expression in ectopic locations, it does enhance its expression. To explore the roles of Sox11 in joint homeostasis, we analyzed adult knee joints in an osteoarthritis mouse model where the medial meniscus and the medial collateral ligament were removed. We also analyzed knee joints from human subjects who underwent total knee replacement surgery. We find that SOX11 is mainly expressed in the weight-bearing areas of knee joints, and its expression is decreased in degraded cartilage during progression of knee osteoarthritis in both mice and humans.

Conclusions

This work implicates SOX11 as a potential regulator of GDF5 expression in joint maintenance and suggests a possible role in the pathogenesis of osteoarthritis.

【 授权许可】

   
2013 Kan et al.; licensee BioMed Central Ltd.

【 图 表 】

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