Fig. 7: Model comparing the alterations in joints of wild-type versus Wnt9a-deficient, hTNFtg/+;Wnt9a∆Prx/−, and hTNFtg/+ animals and pathways utilized by WNT9a to control environmental changes in the joint.
From: Loss of the WNT9a ligand aggravates the rheumatoid arthritis-like symptoms in hTNF transgenic mice
a Compared to the situation in the wild-type, Wnt9a-deficient joints display a mild proinflammatory (slightly increased transcriptional levels of Il1b and Il6) and procatabolic (slightly increased transcriptional levels of Mmp13 and Adamts5) environment. In the hTNFtg/+;Wnt9a∆Prx/− joints, this is converted into a highly inflamed catabolic environment through the activity of TNF. Due to the predispositioning in the Wnt9a-deficient joints, the effects of the TNF transgene are more intense compared to the alteration in hTNFtg/+ joints. b WNT9a acts on the one hand through the Wnt/β-catenin pathway to maintain low transcriptional levels of the proinflammatory factors Il1b and Il6, and of the procatabolic factors Adamts5 and Mmp13 in synovial fibroblasts. On the other hand, WNT9a dampens the activity of the transcription factor NFκB, which is required for osteoclastogenesis downstream of TNF and RANKL.
