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. Summary 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.

Fisetin, a Natural Polyphenol, Ameliorates Endometriosis Modulating Mast Cells Derived NLRP-3 Inflammasome Pathway and Oxidative Stress

“…Several cytokines including IL-1β and TNF-α were reported to be increased in the PF of women with endometriosis [ 38 ]. In addition, the significance of inflammasome and successive excretion of IL-1 family members is supposed to be intricated in the pathogenesis of various diseases [ 39 ]. In that regard, increased levels of IL-1β and TNF-α were found in animals subjected to endometriosis and treated with the vehicle compared to the sham ( Figure 6 A,B).…”

The role of autophagy in SIM mediated anti‐inflammatory osteoclastogenesis through NLRP3 signaling pathway

“…Among the pro‐inflammatory cytokines, IL‐1β strongly induces bone destruction by promoting OC differentiation and activity. IL‐1β is one of the primary members of the IL‐1 family and plays an important role in bone loss following inflammatory infection 51 . In general, LPS stimulates the secretion of various cytokines in the microenvironment, including IL‐1β and TNF‐α, which are involved in LPS‐mediated bone resorption.…”

“…IL‐1β is one of the primary members of the IL‐1 family and plays an important role in bone loss following inflammatory infection. 51 In general, LPS stimulates the secretion of various cytokines in the microenvironment, including IL‐1β and TNF‐α, which are involved in LPS‐mediated bone resorption. However, compared with the LPS group, these events were inhibited by SIM, which indicated that SIM inhibited autophagy‐related proteins and NLRP3‐related proteins expression did not increase in a time‐dependent manner but did fluctuate, thereby decreasing the high levels of autophagy could be a potential strategy for treating and/or preventing inflammation‐related diseases, 52 including inflammatory bone resorption.…”

Senescent cells impair fracture repair through elevating ubiquitin-proteasome system activity in aged mice

“…Collectively, senescent cell derived TGFb regulate the ubiquitination of PDGFRb in CaMPCs and contribute to the impaired fracture repair in aged mice. However, we will not exclude the possibility of SASPs, other than TGFb contribute to the protein ubiquitination, because other increased inflammatory cytokines in callus of aged mice, such as TNFa or IL-1 can activate NF-kB signaling 26,27 , which in turn promote the expression of numerous E3 ligases 14,24,25 . Similarly, UPS has multiple targets in MPCs, because we also found other interesting proteins highly ubiquinated, such as Interferon-induced transmembrane protein (another manuscript to Biorxiv).…”