Drugs Targeting NLRP3 Inflammasome in the Treatment of Diabetic Bone Disorders

Abstract

Background: Growing pieces of evidence demonstrate a close relationship between bone regeneration disorders of diabetic patients and NOD-like receptor thermal protein domain associated protein 3 (NLRP3). Drugs targeting NLRP3 in the treatment of diabetic bone disorders have been heatedly discussed in recent years, and new R&D ideas should be explored.

Objective: This review analyzes molecular mechanisms of how hyperglycemia activates NLRP3 and leads to bone disorders in diabetic patients. Also, this review focuses on the research of drugs targeting NLRP3 inflammasome in the treatment of diabetic bone disorders, and eventually points out the ideas for new drug development.

Results: In diabetic patients, hyperglycemia ultimately increases the expression of NLRP3 inflammasome which cleaves pro-IL-1β into mature IL-1β by caspase-1, leading to impaired bone formation. Drugs targeting NLRP3 inflammasome are divided into two categories. Indirect-acting drugs for NLRP3 inflammasomes include dipeptidyl peptidase-4 inhibitors, lipoxygen A4, epigallocatechin gallate, and vitamin D3. Direct-acting drugs include Glyburide, Dioscin, and Pristimerin.

Conclusion: The presented studies indicate that hyperglycemia is the initiating factor for NLRP3-induced bone disorders in diabetic patients. The main drug targets are the molecules relevant to the assembly and activation of NLRP3 inflammasome. These data may provide a theoretical basis for the further development of drugs targeting NLRP3 inflammasome in the treatment of diabetic bone disorders.

Keywords: Diabetes mellitus; NLRP3 inflammasome; bone disorders; diabetic complications; inflammatory response; new drug development; targeted drugs.