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The production and secretion of these interleukins are regulated by the nucleotide-binding oligomerization domain leucine-rich repeat-containing protein (NLRP3) inflammasome. Uptake of wear particles can lead to mitochondrial damage, the production of reactive oxygen species (ROS), and stress in the endoplasmic reticulum (ER), resulting in an increased production of the ER stress key factor DNA damage-inducible transcript 3 (DDIT3). This factor is known to inhibit the mitophagy of dysfunctional mitochondria, inducing the generation of ROS. All these factors are known to activate the NLRP3 inflammasome. In this study, we investigated the influence of cobalt-chromium-molybdenum particles (CoCr) on the activation of the NLRP3 inflammasome in human osteoblasts (hOBs). Also, this research aimed to examine the impact of particles on mitochondria and the activation of the inflammasome. HOBs were primed with CoCr particles or tumor necrosis factor (TNF). After the incubation period, the cells were again treated with CoCr particles for activation. To test whether particle-induced DDIT3 upregulation has an effect on mitophagy and regulation of the NLRP3 inflammasome in hOBs, cells were additionally treated with the mitophagy agonist carbonyl cyanide-3-chlorophenylhydrazone (CCCP). Treatment of hOBs with metallic particles increased pyroptosis, which was accompanied by the release of IL-18. Further particle exposure damaged and inhibited the degradation of mitochondria. Activating the mitophagy with CCCP in hOBs reduced the inflammatory response to particles and TNF. These findings indicate that particle-induced inflammation can be influenced by maintaining mitochondrial function.<\/jats:p>","DOI":"10.1007\/s10565-025-10087-7","type":"journal-article","created":{"date-parts":[[2025,9,23]],"date-time":"2025-09-23T06:17:25Z","timestamp":1758608245000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Repeated exposure to CoCr28Mo6 particles leads to activation of NLRP3 inflammasome signaling in human osteoblasts"],"prefix":"10.1007","volume":"41","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-1231-7132","authenticated-orcid":false,"given":"Marie-Luise","family":"Sellin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca Marit","family":"Koentopp","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rainer","family":"Bader","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9318-4264","authenticated-orcid":false,"given":"Anika","family":"Jonitz-Heincke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,9,23]]},"reference":[{"issue":"11","key":"10087_CR1","doi-asserted-by":"publisher","first-page":"1201","DOI":"10.1038\/s41423-022-00922-w","volume":"19","author":"A Akbal","year":"2022","unstructured":"Akbal A, Dernst A, Lovotti M, Mangan MSJ, McManus R\u00f3is\u00ednM, Latz E. 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