Inflammation-induced osteogenic signaling promotes calcium phosphate crystal formation in kidneys via MAPK, NF-κB, and smad pathways.

Introduction: Approximately two-thirds of patients with kidney stones exhibit Randall's plaques, interstitial calcium phosphate deposits extending to the papillary surface, serving as stone formation niduses. Although inflammation and osteogenic processes have been implicated in plaque development, their mechanistic connection remains unclear. In vascular calcification, which shares key pathological features with Randall's plaques, pro-inflammatory cytokines upregulate osteogenesis-related proteins to promote calcification. Whether similar signaling occurs in kidneys remains unclear. This study aimed to explore physiopathology and facilitate the development of potential targeted therapies for kidney stones. Methods: HK-2 cells were treated with calcium and pro-inflammatory cytokines to assess calcium deposition and investigate osteogenic transition signaling pathways. Non-cell-based assays were developed to examine the direct effects of osteogenesis-related proteins on specific stages of calcium phosphate crystal formation, including nucleation, growth, and aggregation. To determine whether inflammation is related to osteogenic responses and calcification Results: Discussion: This study provides insight into renal calcification, suggesting that pro-inflammatory cytokines are associated with activation of MAPK, NF-κB, and Smad signaling pathways and upregulation of osteogenesis-related proteins, which may contribute to key stages of crystal formation. Furthermore, this work establishes a novel and time-efficient animal model that offers a valuable platform for investigating the pathogenesis of renal calcification, including processes potentially relevant to Randall's plaque-associated calcification.