Inflammasomes and the IL-1 Family in Bone Homeostasis and Disease.

ABSTRACT

PURPOSE OF REVIEW Inflammasomes are multimeric protein structures with crucial roles in host responses against infections and injuries. The importance of inflammasome activation goes beyond host defense as a dysregulated inflammasome and subsequent secretion of IL-1 family members is believed to be involved in the pathogenesis of various diseases, some of which also produce skeletal manifestations. The purpose of this review is to summarize recent developments in the understanding of inflammasome regulation and IL-1 family members in bone physiology and pathology and current therapeutics will be discussed. RECENT FINDINGS: Small animal models have been vital to help understand how the inflammasome regulates bone dynamics. Animal models with gain or loss of function in various inflammasome components or IL-1 family signaling have illustrated how these systems can impact numerous bone pathologies and have been utilized to test new inflammasome therapeutics. It is increasingly clear that a tightly regulated inflammasome is required not only for host defense but for skeletal homeostasis, as a dysregulated inflammasome is linked to diseases of pathological bone accrual and loss. Given the complexities of inflammasome activation and redundancies in IL-1 activation and secretion, targeting these pathways is at times challenging. Ongoing research into inflammasome-mediated mechanisms will allow the development of new therapeutics for inflammasome/IL-1 diseases.