Bone development and inflammatory disease is regulated by AP-1 (Fos/Jun).

Abstract

The Fos and Jun proteins are members of the AP-1 transcription factor complex, which is a central regulator for many cellular functions. This paper summarises the important functions of Fos proteins in bone development, with special emphasis on the Fos-related proteins Fra-1 and Fra-2. These factors determine the functions of osteoblasts and osteoclasts and regulate cytokine signalling during bone development. Likewise, the Jun proteins control the expression of cytokines and chemokines and are probably causally involved in inflammatory skin diseases such as psoriasis. Investigations into the molecular mechanisms responsible for skin inflammation have revealed that Jun proteins control cytokine expression, such as granulocyte colony-stimulating factor, IL-6 and tumour necrosis factor alpha by transcriptional and posttranscriptional pathways. Finally, the paper discusses the relevance of the Jun-dependent mouse model for psoriasis for preclinical studies in the field of anti-angiogenic therapies.