{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T14:39:49Z","timestamp":1791297589002,"version":"4.1.0"},"reference-count":45,"publisher":"National Academy of Sciences","issue":"36","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2011,9,6]]},"abstract":"<jats:p>\n                    The proinflammatory and catabolic cytokine IL-1\u03b2 has been implicated in the pathogenesis of osteoarthritis (OA) by mediating synovial inflammation and cartilage degeneration. Although synovial macrophages are suggested to be the source of IL-1\u03b2, the mechanism remains unclear. Ectopic deposition of hydroxyapatite (HA) crystals in joints is closely associated with OA and other arthropathies, but the precise role of HA in arthritis pathogenesis has not been clearly demonstrated. Here we show that HA crystals of a particular size and shape can stimulate robust secretion of proinflammatory cytokines IL-1\u03b2 and IL-18 from murine macrophages in a NLRP3 inflammasome-dependent manner. HA-induced inflammasome activation is dependent on potassium efflux, generation of reactive oxygen species (ROS), and lysosomal damage, but independent of cell death. Mice lacking the inflammasome components are protected against HA-induced neutrophilic inflammation in the air-pouch model of synovitis, and they show decreased joint pathology accompanying spontaneous HA deposition in the\n                    <jats:italic>ank<\/jats:italic>\n                    -deficient mouse model of arthritis. Moreover, calcium crystal positive synovial fluids from some OA patients exhibited inflammasome-stimulatory activity in vitro. These results demonstrate that the NLRP3 inflammasome mediates the pathological effect of HA crystals in vitro and in vivo and suggest a critical role for the inflammasome in the pathogenesis of OA.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1111101108","type":"journal-article","created":{"date-parts":[[2011,8,19]],"date-time":"2011-08-19T22:47:12Z","timestamp":1313794032000},"page":"14867-14872","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":230,"title":["NLRP3 inflammasome plays a critical role in the pathogenesis of hydroxyapatite-associated arthropathy"],"prefix":"10.1073","volume":"108","author":[{"given":"Chengcheng","family":"Jin","sequence":"first","affiliation":[{"name":"Departments of aImmunobiology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Frayssinet","sequence":"additional","affiliation":[{"name":"Le Gaillard, 31470 St Lys, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Pelker","sequence":"additional","affiliation":[{"name":"Orthopaedics and Rehabilitation and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diane","family":"Cwirka","sequence":"additional","affiliation":[{"name":"Orthopaedics and Rehabilitation and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Hu","sequence":"additional","affiliation":[{"name":"Departments of aImmunobiology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agn\u00e8s","family":"Vignery","sequence":"additional","affiliation":[{"name":"Orthopaedics and Rehabilitation and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie C.","family":"Eisenbarth","sequence":"additional","affiliation":[{"name":"Departments of aImmunobiology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard A.","family":"Flavell","sequence":"additional","affiliation":[{"name":"Departments of aImmunobiology and"},{"name":"Howard Hughes Medical Institute, Yale University, New Haven, CT 06520; and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2011,8,19]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1186\/ar2655"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11926-007-0019-9"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.27290"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1080\/03008200802148355"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.3899\/jrheum.080346"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.10260"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1012743108"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2008.01.031"},{"key":"e_1_3_3_9_2","first-page":"469","article-title":"Interleukin-18 induces apoptosis in human articular chondrocytes","volume":"22","author":"John T","year":"2007","unstructured":"T John, B Kohl, A Mobasheri, W Ertel, M Shakibaei, Interleukin-18 induces apoptosis in human articular chondrocytes. Histol Histopathol 22, 469\u2013482 (2007).","journal-title":"Histol Histopathol"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1097\/00002371-200203001-00009"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2010.01.040"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10875-010-9440-3"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature04516"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.2741\/1623"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11926-009-0020-6"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.2741\/1549"},{"key":"e_1_3_3_17_2","first-page":"39","volume-title":"Emergency Orthopedics: The Extremities","author":"Simon RR","year":"2001","unstructured":"RR Simon, SJ Koenigsknecht Emergency Orthopedics: The Extremities (McGraw-Hill, 4th Ed, New York), pp. 39 (2001).","edition":"4"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11926-003-0070-0"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0142-9612(03)00089-9"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1053\/joca.1998.0113"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2009.12.004"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature02664"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature04515"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature01991"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20071087"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0713552"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.21238"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1186\/ar143"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/4.7.1225"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.bor.0000209432.36355.6e"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1359\/jbmr.060515"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.289.5477.265"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11926-009-0021-5"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1001284"},{"key":"e_1_3_3_35_2","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1002\/art.30147","article-title":"Octacalcium phosphate (OCP) crystals induce inflammation in vivo through IL-1 but independent of the NLRP3 inflammasome","volume":"63","author":"Narayan S","year":"2010","unstructured":"S Narayan, et al., Octacalcium phosphate (OCP) crystals induce inflammation in vivo through IL-1 but independent of the NLRP3 inflammasome. 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