Studies from our lab and others strongly suggest that A-Beta compromises the function of Wnt proteins
. Indeed, we discovered that A-Beta promotes the synthesis of Dickkopf-1 (Dkk1), a secreted Wnt antagonist and this protein mediates the toxic effect(s) of A-Beta on brain synapses.
constitute a family of secreted cysteine-rich glycoproteins that exhibit distinct expression patterns in the embryo and adult organisms (1).
The expression of various Wnt proteins
was studied during odontogenesis (Sarkar & Sharpe, 1999), and also during general facial development (Geetha-Loganathan et al, 2009), while the Wnt/[beta]-catenin way was studied on tooth germs (Liu et al, 2008; Lo Muzio et al, 2009; Fujimori et al, 2010; Wang et al, 2014).
However, the inflammatory roles of Wnt proteins
vary widely depending on the tissue- and pathophysiological-specific contexts.
bind to a receptor/coreceptor complex on the plasma membrane, which consists of LRP5/6 and Frizzled proteins.
In particular, skin wounds express various Wnt proteins
with transcripts of Wnt-1, -3a, -4, -5a, and -10b .
stimulate intracellular signaling pathways, regulate gene expression in the nucleus, and determine cell fate.
are a group of cysteine-rich glycosylated proteins that are able to stimulate the growth of specific tissues and play an important role in the regulation of various cellular processes such as cell proliferation and differentiation (10-12).
promote new bone formation in inflammatory arthritis.
Even though Wnt proteins
are difficult to manipulate, their ability to reverse intestinal stem cell aging suggests a pathway that clinicians may eventually be able to target.
In bone, DKK-1 and SOST proteins act to halt the Wnt cascade, either binding to LRP4/5/6 and stopping its connections with the Wnt-Fzd complex or connecting with Wnt proteins
, blocking their roles entirely .
The Wnt signaling pathway including LRP5 and Wnt proteins
regulate osteoblastic activity and bones mass.