FLNB acts as a bridge for TGFβ/BMP signaling crosstalk through i-Smads and is key for the critical balance in TGFβ/BMP signaling that maintains the IVD. These most effective improvements resulted from specific inhibition of TGFβ and p38 signaling activation. Inhibition of canonical and noncanonical TGFβ/BMP pathway activity restored Flnb −/− IVD morphology. Through the use of small molecule inhibitors in an ex vivo spine model, TGFβ/BMP signaling was modulated to design a targeted treatment for SCT and disc degeneration. The data demonstrated that FLNB interacts with inhibitory Smads 6 and 7 (i-Smads) to regulate TGFβ/BMP signaling and that loss of FLNB produces increased TGFβ receptor activity and decreased Smad 1 ubiquitination. In this study, the role of FLNB in the TGFβ/BMP pathway was elucidated using in vitro, in vivo, and ex vivo treatment methodologies.
![little disc by the mouse little disc by the mouse](https://i.ebayimg.com/images/g/FFsAAOSwItddwEGg/s-l64.jpg)
This resulted from alterations in the TGFβ/BMP signaling pathway that included increased canonical TGFβ and noncanonical BMP signaling.
#LITTLE DISC BY THE MOUSE FULL#
Utilizing a FLNB knockout mouse, we showed that the vertebral fusions in SCT evolved from intervertebral disc (IVD) degeneration and ossification of the annulus fibrosus (AF), eventually leading to full trabecular bone formation.
![little disc by the mouse little disc by the mouse](https://i.gr-assets.com/images/S/compressed.photo.goodreads.com/books/1413757010i/1294937._UY630_SR1200,630_.jpg)
![little disc by the mouse little disc by the mouse](http://www.littlebcakes.com/wp-content/uploads/2014/02/Toy-Story-Cake-Ideas-682x1024.jpg)
Spondylocarpotarsal syndrome (SCT) is a rare musculoskeletal disorder characterized by short stature and vertebral, carpal, and tarsal fusions resulting from biallelic nonsense mutations in the gene encoding filamin B (FLNB).