Recent developments on BMPs and their antagonists in inflammatory bowel diseases

Inflammatory bowel diseases (IBDs), including ulcerative colitis, and Crohn's disease, are intestinal disorders characterized by chronic relapsing inflammation. A large proportion of patients with IBD will progress to develop colitis-associated colorectal cancer due to the chronic intestinal inflammation. Biologic agents that target tumour necrosis factor-& alpha;, integrin & alpha;4 & beta;7, and interleukin (IL)12/23p40 have been more successful than conventional therapies in treating IBD. However, drug intolerance and loss of response are serious drawbacks of current biologics, necessitating the development of novel drugs that target specific pathways in IBD pathogenesis. One promising group of candidate molecules are bone morphogenetic proteins (BMPs), members of the TGF-& beta; family involved in regulating morphogenesis, homeostasis, stemness, and inflammatory responses in the gastrointestinal tract. Also worth examining are BMP antagonists, major regulators of these proteins. Evidence has shown that BMPs (especially BMP4/6/7) and BMP antagonists (especially Gremlin1 and follistatin-like protein 1) play essential roles in IBD pathogenesis. In this review, we provide an updated overview on the involvement of BMPs and BMP antagonists in IBD pathogenesis and in regulating the fate of intestinal stem cells. We also described the expression patterns of BMPs and BMP antagonists along the intestinal crypt-villus axis. Lastly, we synthesized available research on negative regulators of BMP signalling. This review summarizes recent developments on BMPs and BMP antagonists in IBD pathogenesis, which provides novel insights into future therapeutic strategies.

Automated summary

Inflammatory bowel diseases (IBDs) are chronic intestinal disorders characterized by relapsing inflammation, which can lead to colitis-associated colorectal cancer. Biologic agents targeting specific pathways in IBD pathogenesis have shown more success than conventional therapies. Bone morphogenetic proteins (BMPs) and BMP antagonists have been identified as promising candidates for IBD treatment. This review provides an updated overview on the involvement of BMPs and BMP antagonists in IBD pathogenesis and their role in regulating intestinal stem cells, highlighting potential therapeutic strategies.