This study is by Hiroki Yokota of LSJL fame:

In Vitro and in Silico Analysis of ADAMTS5 Transcription in Human Chondrocytes

“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 ADAMTS5 was at least in part stimulated by p38 MAPK and IL1β, while Lrp5 acted as a suppressor of their upregulation. Regulatory network analysis using an algorithm predicted the potential involvement of Wnt3a, Myc and CCAAT/Enhancer-Binding Protein β (CEBPB). A secretary factor such as Wnt3a might be involved in Lrp5-mediated homeostasis of ADAMTS5.”

“ow-density-Lipoprotein Receptor-Related Protein 5 (Lrp5) is a co-receptor in the canonical Wnt signaling pathway and global deletion of Lrp5 in mice as well as conditional deletion in osteocytes results in a deficiency in load-driven bone formation and presents a phenotype of low bone mass”

” Mice deficient in ADAMTS5 are protected from cartilage erosion in mouse models of osteoarthritis”<-however erosion of the cartilage is important for endochondral ossification.

“In response to treatment with Lrp5 siRNA, mRNA levels of to 6 interleukin genes (IL6, IL1β, IL12A, IL15, IL18, IL16) were elevated while IL8 mRNA was suppressed”

“Compared with Lrp5 siRNA, IL1β treatment caused a similar elevation to mRNA abundance of IL6, IL1β and ADAMTS5. However, administration of IL1β did not elevate the mRNA levels of IL12A, IL15, IL18, IL8 and IL16”

“both sequences of LRP5 siRNA elevated the phosphorylation of p38 MAPK. Applying p38 siRNA decreased total and phosphorylated p38 MAPK, while a double knockdown with LRP5 siRNA showed a slight recovery in the phosphorylated p38 MAPK level. ADAMTS5 mRNA levels decreased after p38 siRNA. Double knockdown of both p38 siRNA and LRP5 siRNA slightly decreases the elevation of ADAMTS5 mRNA caused by a single knockdown of just LRP5 siRNA.”