BMP signaling and negative regulation in bone formation

BMP signaling and negative regulation in bone formation. Smad-dependent-BMP signaling binds to receptor type II (R-II) and receptor type I (R-I) and then the signaling transduces to their Smads. Activated Smads form a complex with Smad4 and then translocate into the nucleus where they interact with other transcription factors to trigger target gene expression. Neogenin regulates BMP receptor association and Smad1/5/8 signaling. Activated Smads regulate expression of transcriptional factors and transcriptional coactivators important in osteoblasts (Dlx5, Runx2 and Osx). Smad6 binds type I BMP receptor and prevents Smad1/5/8 to be activated. Non-Smad-dependent TAK1 signaling pathway also regulates bone formation. The interplay between BMPs and Wnt signaling affects bone formation . BMPRIA signaling upregulates Sost expression primarily through Smad-dependent signaling, while it upregulates DKK1 through Smad-dependent and non-Smad-dependent signaling. Both Sost and DKK1 inhibit canonical Wnt signaling, leading to a decrease in bone mass. P: phosphorylation; Ub: ubiquitination.

Publication

TGF-β and BMP Signaling in Osteoblast Differentiation and Bone Formation. (2012) Guiqian Chen, et al. Int J Biol Sci. 2012;8(2):272-288. Figure: F2. All organisms Mus musculus Rattus norvegicus Drosophila melanogaster Homo sapiens Gallus gallus Danio rerio

Disease mentions