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Cell Dev. Biol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Approximately two-thirds of patients with kidney stones exhibit Randall\u2019s 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\u2019s 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      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\n                      <jats:italic>in vivo<\/jats:italic>\n                      , a novel rat model of renal calcium deposition was established by combining a high-calcium diet with unilateral ureteral obstruction surgery. Renal calcium deposits were also evaluated.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      <jats:italic>In vitro<\/jats:italic>\n                      , pro-inflammatory cytokines enhanced calcium-induced mineralization in renal tubular cells and were associated with the activation of MAPK, NF-\u03baB, and Smad signaling pathways, along with the upregulation of osteogenesis-related proteins. These proteins exerted direct, stage-specific effects on calcium phosphate crystal nucleation, growth, and aggregation. In our novel rat model, inflammation enhanced renal calcium deposition and upregulated osteogenic markers within 1 month. The positive correlation between the renal expression of inflammatory cytokines and osteoblast markers mirrored the\n                      <jats:italic>in vitro<\/jats:italic>\n                      findings.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>This study provides insight into renal calcification, suggesting that pro-inflammatory cytokines are associated with activation of MAPK, NF-\u03baB, 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\u2019s plaque\u2013associated calcification.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fcell.2026.1831072","type":"journal-article","created":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T05:37:53Z","timestamp":1782797873000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Inflammation-induced osteogenic signaling promotes calcium phosphate crystal formation in kidneys via MAPK, NF-\u03baB, and smad pathways"],"prefix":"10.3389","volume":"14","author":[{"given":"Yi-Shiou","family":"Tseng","sequence":"first","affiliation":[{"name":"Division of Traumatology, Department of Surgery, Far Eastern Memorial Hospital","place":["New Taipei, Taiwan"]},{"name":"Division of Urology, Department of Surgery, Far Eastern Memorial Hospital","place":["New Taipei City, Taiwan"]},{"name":"Department of Chemical Engineering and Materials Science, Yuan Ze University","place":["Taoyuan City, Taiwan"]},{"name":"Graduate Institute of Medicine, Yuan Ze University","place":["Taoyuan City, Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hsing-I","family":"Tseng","sequence":"additional","affiliation":[{"name":"Division of Traumatology, Department of Surgery, Far Eastern Memorial Hospital","place":["New Taipei, Taiwan"]},{"name":"Department of Medical Research, Far Eastern Memorial Hospital","place":["New Taipei, Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Po-Wen","family":"Ku","sequence":"additional","affiliation":[{"name":"Division of Urology, Department of Surgery, Far Eastern Memorial Hospital","place":["New Taipei City, Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huei-Pin","family":"Lai","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Metabolism, Department of Internal Medicine, Far Eastern Memorial Hospital","place":["New Taipei City, Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting-Hui","family":"Chang","sequence":"additional","affiliation":[{"name":"Division of Allergy Immunology and Rheumatology, Department of Internal Medicine, Far Eastern Memorial Hospital","place":["New Taipei City, Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen-Po","family":"Chuang","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Cardiovascular Center, Far Eastern Memorial Hospital","place":["New Taipei City, Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiann-Ming","family":"Wu","sequence":"additional","affiliation":[{"name":"Division of General Surgery, Department of Surgery, Far Eastern Memorial Hospital","place":["New Taipei City, Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,30]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"e003905","DOI":"10.1161\/JAHA.112.003905","article-title":"Bone morphogenetic protein-2 decreases microRNA-30b and microRNA-30c to promote vascular smooth muscle cell calcification","volume":"1","author":"Balderman","year":"2012","journal-title":"J. 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