Hiroki Yokota
Tanzania
Research Article
In Vitro and in Silico Analysis of ADAMTS5 Transcription in Human Chondrocytes
Author(s): Kazunori Hamamura, Andy Chen, Nancy Tanjung, Hui B Sun and Hiroki YokotaKazunori Hamamura, Andy Chen, Nancy Tanjung, Hui B Sun and Hiroki Yokota
Osteoarthritis is a major cause of disability in the adult population. Exercise is commonly prescribed, but the mechanisms underlying mechanotransduction of joint tissues are not well understood. Since Lrp5 is an important mechano-sensitive receptor in Wnt signaling, we examined its role in the mRNA expression of A Disintegrin and Metalloproteinase with Thrombospondin Motifs 5 (ADAMTS5), a major proteolytic aggrecanase that degrades extracellular matrix in articular cartilage. Using genome-wide expression data for C28/I2 chondrocytes with and without Lrp5-specific siRNA, we employed a systems biology approach and built a regulatory network model. Experimental data revealed that silencing Lrp5 significantly altered Wnt signaling gene expression and elevated the mRNA level of ADAMTS5 and several cytokines. A series of experiments using RNA interference showed that the expression of ADAM.. View More»
