Activation of the noncanonical inflammasome-GSDMD pathway triggers pyroptosis in bone marrow and promotes periosteal bone formation
Year: 2025
Type: article
Abstract: Evidence indicating that inflammation is commonly associated with ectopic osteogenesis in certain autoimmune and infectious conditions challenges the dogma that inflammatory responses always suppress bone formation. In this study, we find that systemic administration of lipopolysaccharide (LPS) to mice causes not only inflammation in bone marrow, as expected, but also stimulates periosteal bone formation. This response can be reproduced in vitro as bone marrow supernatants from LPS-treated mice induce robust osteogenesis of osteoprogenitors compared to supernatants from PBS-treated counterparts. Periosteal bone accrual is partly dependent on periosteal leptin receptor-positive (LepR)+ osteoprogenitors but not bone marrow LepR+ or adiponectin (Adq)+ osteoprogenitors and correlates with pyroptosis within bone marrow. Consistent with the dependence of periosteal osteogenesis on pyroptosis, this response is slightly attenuated in Nlrp3-/- or caspase-1-/- mice but significantly inhibited in caspase-11-/-, caspase-1-/-;caspase-11-/-, or Gsdmd-/- mice. Our study reveals a novel role for pyroptosis in which lysed cells release intracellular contents that stimulate osteoprogenitors and promote osteogenic differentiation within the periosteal compartment.
DOI: 10.1093/jbmr/zjaf197
Authors: Wei Zou, Chun Wang, Yongjia Li, Wentong Jia, Steven L Teitelbaum, Gabriel Mbalaviele
Institution: Washington University in St. Louis
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $3,780
Funders: U.S. Department of Defense, American Heart Association, Foundation for Barnes-Jewish Hospital, National Institutes of Health, Musculoskeletal Research Center, Washington University in St. Louis, National Institute of Allergy and Infectious Diseases, National Institute of Arthritis and Musculoskeletal and Skin Diseases
Awards: Cabinet microCT System for Musculoskeletal Specimen Imaging, Role of mitochondria transfer in myocardial infarction and associated systemic inflammation, Mechanisms of AVB3 Integrin Mediated Bone Resorption, G4296882399, G9000004556, G9000016852, G9000022199, G9000069669, G9000076815, G9000175160, G9000217772, Differential Inflammasome Regulation in the pathogenesis of S. aureus osteomyelitis, Hepatic steatosis promotes liver metastasis, G952867865
OpenAlex ID: W4417448234