About GREM / Gremlin:
Gremlin inhibits the signaling pathways in the TGF Beta. This results in bone morphogenesis and is key to understanding certain bone conditions and some cancers. Bone conditions that present signs of increased bone growth or density could be related to the Gremlin inhibitor; similarly, a lack of bone growth could be linked.
The gremlin protein is a glycoprotein contained in the family of DAN. It is a 184 amino acid protein and has a cysteine knot-secreted structure. It was first found in a differential screening. Initially, it was identified as a down-regulated gene in rat embryo fibroblasts. The protein was previously known as Drm.
Gremlin is thought to interact with bone morphogenetic proteins (BMPs) and influence their potential in the Beta signaling pathway. It usually inhibits the BMP2 and BMP4 limb buds and forms an automated feedback system. In the limb buds, the Gremlin protein facilitates the transcriptional up-regulation of the fibroblast growth factors. This helps to regulate the formation of limb buds.
It's thought the gremlin protein plays a vital role in the formation of certain life-changing diseases such as cancer and bone formation. Studies of cancerous tissues show that the presence of gremlin protein helps them survive specific cancer cells and aids their proliferation. Cancers of this kind are uterine cervix, lung, ovary, kidney, breast, colon, pancreas, and sarcoma carcinoma.
In relation to bone structure and growth, gremlin protein is shown to assist in trabecular bone volume. It can cause an overexpression of bone formation that might be symptomatic of bone growth diseases. This process has been observed in mice, but not enough is known to confidently predict outcomes for humans.