Searchable abstracts of presentations at key conferences on calcified tissues
Bone Abstracts (2014) 3 PP178 | DOI: 10.1530/boneabs.3.PP178

ECTS2014 Poster Presentations Chondrocytes and cartilage (9 abstracts)

LDL receptor-related protein 5 governs Wnt-mediated osteoarthritic cartilage destruction

Yunhyun Huh 1 , Jeong-Tae Koh 2 , Min-Suk Kook 2 & Je-Hwang Ryu 2


1Gwangju Institute of Science and Technology, Gwangju, Republic of Korea; 2Chonnam National University, Gwangju, Republic of Korea.


Introduction: Wnt ligands bind to LDL receptor-related protein (LRP) 5 or −6, triggering a cascade of downstream events that include β-catenin signaling. Here, we explored the roles of LRP5 in interleukin (IL)-1β- or Wnt-mediated osteoarthritic (OA) cartilage destruction in mice.

Methods: The expression levels of LRP5, Type II collagen, and catabolic factors were determined in mouse articular chondrocytes, human OA cartilage, and mouse experimental OA cartilage. Experimental OA in WT, Lrp5 total knockout (Lrp5−/−) and chondrocyte-specific knockout (Lrp5fl/fl;Col2a1-cre) mice was caused by aging, destabilization of the medial meniscus (DMM), or intra-articular injection of collagenase. The role of LRP5 was confirmed in vitro by siRNA-mediated knockdown of Lrp5 or in Lrp5−/− cells treated with IL-1β or Wnt proteins.

Results: IL-1β treatment increased the expression of LRP5 (but not LRP6) via JNK and NF-κB signaling. LRP5 was up-regulated in human and mouse OA cartilage, and Lrp5 deficiency in mice inhibited cartilage destruction. Treatment with IL-1β or Wnt decreased the level of Col2a1 and increased those of Mmp3 or Mmp13, whereas Lrp5 knockdown ameliorated these effects. In addition, we found that the functions of LRP5 in arthritic cartilage were subject to transcriptional activation by β-catenin. Moreover, Lrp5−/− and Lrp5fl/fl; Col2a1-cre mice exhibited decreased cartilage destruction (and related changes in gene expression) in response to experimental OA.

Conclusion: Our findings indicate that LRP5 (but not LRP6) plays an essential role in Wnt/β-catenin-signaling-mediated OA cartilage destruction in part by regulating the expression levels of type II collagen, MMP3, and MMP13.

Volume 3

European Calcified Tissue Society Congress 2014

Prague, Czech Republic
17 May 2014 - 20 May 2014

European Calcified Tissue Society 

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