The Activating Protein-1 Transcriptional Complex: Essential and Multifaceted Roles in Bone

Abstract

The activating protein-1 (AP-1) family of transcriptional mediators is composed of dimers of Jun and Fos family members that have other potential partners such as the activating transcription factor (ATF) and musculoaponeurotic fibrosarcoma (Maf) protein families as well. AP-1 is one of the first and most well-characterized transcriptional mediators known with noted impact described in the literature for most tissues in the body. The skeletal impact of AP-1 has been intensively investigated, and extensive information exists for the role of various AP-1 proteins in osteoblast and chondrocyte activities in vitro. Numerous genes important in skeletal biology such as the receptor activator of nuclear factor (NF)-ϰB-ligand (RANKL), osteocalcin (OCN), runx2, collagens, and bone morphogenetic proteins (BMPs) contain AP-1 sites in their promoters, and key hormonal controls of skeletogenesis rely on AP-1 for their activities. Gene-targeted murine models with loss and gain of function for the various AP-1 family members have been particularly informational in the understanding of AP-1 in bone. The complex signaling network that is emerging for osteoclast differentiation reveals a critical role for AP-1. The context of the AP-1, the composition of the dimerizations and the temporal presentation of the downstream activities of AP-1 are integral to the balance of osteoblast and osteoclast function.